Organisational Buying Decision Process for Biodegradable Implants

Työn tavoitteena oli selvittää organisaation ostopäätösprosessi, kun tuotteina ovat biohajoavat kasvo- ja kallokirurgian implantit. Ensin selvitettiin biohajoavien implanttien markkinapotentiaalia, biohajoavien materiaalien lisäksi implanttien valmistuksessa käytettäviä muita materiaaleja sekä implanteilta vaadittavia ominaisuuksia kirjallisuuden ja internetin sekä asiantuntijahaastatteluiden avulla. Kirjallisuuden avulla selvitettiin myös organisaatioiden ostopäätösprosessien yleisiä piirteitä ja vaiheita. Biohajoavien kasvo- ja kallokirurgian implanttien ostopäätösprosessia tutkittiin kirjallisen kyselytutkimuksen avulla, joka oli suunnattu alan asiantuntijoille Euroopassa, Yhdysvalloissa sekä Kanadassa. Tutkimuksessa selvitettiin mm. tärkeimpiä käytettävien implanttien materiaalivalintaan vaikuttavia kriteereitä, ostopäätösprosessiin osallistuvia organisaation jäseniä, sekä heidän roolejaan päätöksenteossa, implantteja koskevan informaation etsintää sekä ostopäätösprosessin vaiheita. Kirjallisuudesta, internetistä, asiantuntijahaastatteluista ja kyselytutkimuksesta saatu tieto koottiin vuokaaviomalliksi, joka kuvaa kasvo- ja kallokirurgian implanttien ostopäätösprosessia organisaatioissa. Lopuksi esitettiin myös ehdotuksia markkinointisuunnitelmaan sekä jatkotutkimusehdotukset.

Dynamic arrest in polymer melts: competition between packing and intramolecular barriers

We present molecular dynamics simulations of a simple model for polymer melts with intramolecular barriers. We investigate structural relaxation as a function of the barrier strength. Dynamic correlators can be consistently analyzed within the framework of the mode coupling theory of the glass transition. Control parameters are tuned in order to induce a competition between general packing effects and polymer-specific intramolecular barriers as mechanisms for dynamic arrest. This competition yields unusually large values of the so-called mode coupling theory exponent parameter and rationalizes qualitatively different observations for simple bead-spring and realistic polymers. The systematic study of the effect of intramolecular barriers presented here also establishes a fundamental difference between the nature of the glass transition in polymers and in simple glass formers.

Peripheral Nerve Repair: Multimodal Comparison of the Long-Term Regenerative Potential of Adipose Tissue-Derived Cells in a Biodegradable Conduit.

Tissue engineering is a popular topic in peripheral nerve repair. Combining a nerve conduit with supporting adipose-derived cells could offer an opportunity to prevent time-consuming Schwann cell culture or the use of an autograft with its donor site morbidity and eventually improve clinical outcome. The aim of this study was to provide a broad overview over promising transplantable cells under equal experimental conditions over a long-term period. A 10-mm gap in the sciatic nerve of female Sprague-Dawley rats (7 groups of 7 animals, 8 weeks old) was bridged through a biodegradable fibrin conduit filled with rat adipose-derived stem cells (rASCs), differentiated rASCs (drASCs), human (h)ASCs from the superficial and deep abdominal layer, human stromal vascular fraction (SVF), or rat Schwann cells, respectively. As a control, we resutured a nerve segment as an autograft. Long-term evaluation was carried out after 12 weeks comprising walking track, morphometric, and MRI analyses. The sciatic functional index was calculated. Cross sections of the nerve, proximal, distal, and in between the two sutures, were analyzed for re-/myelination and axon count. Gastrocnemius muscle weights were compared. MRI proved biodegradation of the conduit. Differentiated rat ASCs performed significantly better than undifferentiated rASCs with less muscle atrophy and superior functional results. Superficial hASCs supported regeneration better than deep hASCs, in line with published in vitro data. The best regeneration potential was achieved by the drASC group when compared with other adipose tissue-derived cells. Considering the ease of procedure from harvesting to transplanting, we conclude that comparison of promising cells for nerve regeneration revealed that particularly differentiated ASCs could be a clinically translatable route toward new methods to enhance peripheral nerve repair.

Study on the removal of biodegradable NOM from seawater using biofiltration

Despite the low biodegradability of seawater NOM, problems associated with biofouling are common in facilities that handle seawater. In this work, a fixed-film aerobic biofilter is proposed as an effective unit for preventing biofouling in such facilities. A packed-bed biofilter with an EBCT = 6 - 11 min was employed. The results demonstrated that the DOC is reduced by 6% and the BOD7 is reduced up to 15%. The LC-OCD analysis revealed that biofiltration abates the LMW neutrals and biopolymer fractions by 33 and 17%, respectively. However, the fractionation with UF membrane showed that the biofiltration process is able to degrade the more biodegradable compounds that have molecular weights that are greater than 1 kDa and compounds with molecular weights of less than 1 kDa. After biofiltration, the biological activity measured in terms of ATP removal was reduced by 60%. Finally, a test to evaluate the biofilm formation capacity of a water sample revealed reductions of ~94% when comparing biofiltered and non-biofiltered seawater. Therefore, a fixed-film aerobic biofiltration process could be a useful treatment for the removal of biodegradable organic matter from seawater and for improving the water quality in terms of less biofilm formation capacity.

Macroporous Scaffolds for Bone Engineering. Studies on Cell Culture and Ectopic Bone Formation

Bone engineering is a rapidly developing area of reconstructive medicine where bone inducing factors and/or cells are combined with a scaffold material to regenerate the structure and function of the original tissue. The aim of this study was to compare the suitability of different macroporous scaffold types for bone engineering applications. The two scaffold categories studied were a) the mechanically strong and stable titanium fiber meshes and b) the elastic and biodegradable porous polymers. Furthermore, bioactive modifications were applied to these basic scaffold types, and their effect on the osteogenic responses was evaluated in cell culture and ectopic bone formation studies. The osteogenic phenotype of cultured cell-scaffold constructs was heightened with a sol-gel derived titania coating, but not with a mixed titania-silica coating. The latter coating also resulted in delayed ectopic bone formation in bone marrow stromal cell seeded scaffolds. However, the better bone contact in early implantation times and more even bone tissue distribution at later times indicated enhanced osteoconductivity of both the coated scaffold types. Overall, the most promising bone engineering results were obtained with titania coated fiber meshes. Elastic and biodegradable poly(ε-caprolactone/D,L-lactide) based scaffolds were also developed in this study. The degradation rates of the scaffolds in vitro were governed by the hydrophilicity of the polymer matrix, and the porous architecture was controlled by the amount and type of porogen used. A continuous phase macroporosity was obtained using a novel CaCl2 • 6H2O porogen. Dynamic culture conditions increased cell invasion, but decreased cell numbers and osteogenicity, within the scaffolds. Osteogenic differentiation in static cultures and ectopic bone formation in cell seeded scaffolds were enhanced in composites, with 30 wt-% of bioactive glass filler.

High-Performance-Tensile-Strength Alpha-Grass Reinforced Starch-Based Fully Biodegradable Composites

Though there has been a great deal of work concerning the development of natural fibers in reinforced starch-based composites, there is still more to be done. In general, cellulose fibers have lower strength than glass fibers; however, their specific strength is not far from that of fiberglass. In this work, alpha-fibers were obtained from alpha-grass through a mild cooking process. The fibers were used to reinforce a starch-based biopolymer. Composites including 5 to 35% (w/w) alpha-grass fibers in their formulation were prepared, tested, and subsequently compared with those of wood- and fiberglass-reinforced polypropylene (PP). The term “high-performance” refers to the tensile strength of the studied composites and is mainly due to a good interphase, a good dispersion of the fibers inside the matrix, and a good aspect ratio. The tensile strength of the composites showed a linear evolution for fiber contents up to 35% (w/w). The strain at break of the composites decreased with the fiber content and showed the stiffening effects of the reinforcement. The prepared composites showed high mechanical properties, even approaching those of glass fiber reinforced composites

Produção biotecnológica de poli-hidroxialcanoatos para a geração de polímeros biodegradáveis no Brasil

In recent years, several studies have been developed in Brazil to produce biodegradable materials. A particular family of bacterial polymers, the polyhydroxyalkanoates (PHA), has received special attention. PHAs are thermoplastic, biodegradable, biocompatible, are synthesised from renewable resources and can substitute petrochemical plastics in some applications. Different aspects have been focused to increase productivity and to reduce the cost of PHA production: bacterial improvement, use of industrial by-products as raw material, bioreactor design, process operation strategies, downstream process, mathematical modelling, polymer characterisation, application and biodegradability of blends. A production process was transferred to industry and studies to produce new PHA by controlling monomer composition are in progress. All these aspects are presented in this review.

Micro- and nanostructuring of poly(ethylene-2,6-naphthalate) surfaces, for biomedical applications, using polymer replication techniques

Here we investigate the formation of superficial micro- and nanostructures in poly(ethylene-2,6-naphthalate) (PEN), with a view to their use in biomedical device applications, and compare its performance with a polymer commonly used for the fabrication of these devices, poly(methyl methacrylate) (PMMA). The PEN is found to replicate both micro- and nanostructures in its surface, albeit requiring more forceful replication conditions than PMMA, producing a slight increase in surface hydrophilicity. This ability to form micro/nanostructures, allied to biocompatibility and good optical transparency, suggests that PEN could be a useful material for production of, or for incorporation into, transparent devices for biomedical applications. Such devices will be able to be autoclaved, due to the polymer's high temperature stability, and will be useful for applications where forceful experimental conditions are required, due to a superior chemical resistance over PMMA.

Fosfatos de cálcio de interesse biológico: importância como biomateriais, propriedades e métodos de obtenção de recobrimentos

For decades the Hydroxyapatite (HA) was only bioceramic of calcium phosphate system used for bone replacement and regeneration, due to its similarity to the mineral phase of bones and teeth. Because its slow degradation, other calcium phosphate classified as biodegradable started to awaken interest, such as: amorphous calcium phosphate (ACP), octacalcium phosphate (OCP) and tricalcium phosphate (TCP). This work presents the evolution of the use of other calcium phosphates due to their better solubility than the HA, comparing their main physical-chemical and biological properties. Are also presented the main methods used to obtain bioceramic coatings on metal and polymer surfaces.

Development and validation of a high performance liquid chromatographic method for determination of cyclosporine-A from biodegradable intraocular implants

An HPLC method was developed and validated aiming to quantify the cyclosporine-A incorporated into intraocular implants, released from them; and in direct contact with the degradation products of PLGA. The separation was carried out in isocratic mode using acetonitrile/water (70:30) as mobile phase, a C18 column at 80 ºC and UV detection at 210 nm. The method provided selectivity based on resolution among peaks. It was linear over the range of 2.5-40.0 µg/mL. The quantitation and detection limits were 0.8 and 1.2 µg/mL, respectively. The recovery was 101.8% and intra-day and inter-day precision was close to 2%.

In situ synthesis of nanoclay filled polyethylene using polymer supported metallocene catalyst system

In situ ethylene polymerizations were performed using bis(cyclopentadiene)titanium dichloride supported on polyethersulfone as catalyst. The bis(cyclopentadiene)titanium dichloride supported on polyethersulfone catalyst activity estimated by ethylene polymerization was 360 kgPE/molTi/h. During polymerization the fillers used were montmorillionite nanoclays having surface modifications with 35-45 wt% dimethyl dialkyl(14-18)amine (FA) and 25-30 wt% trimethyl stearyl ammonium (FB). These fillers were pretreated with methylaluminoxine (MAO; cocatalyst) for better dispersion onto the polymer matrix. The formation of polyethylene within the whole matrix was confirmed by FTIR studies. It was found that the nature of nanofiller did not have any remarkable effect on the melting characteristics of the polymer. TGA study indicates that nanoclay FB filled polyethylene has higher thermal stability than nanoclay FA filled polyethylene. The melting temperature of the obtained polyethylenes was 142 ºC, which corresponds to that synthesized by the polyether sulfone supported catalyst.

Characterization and in vitro release of cyclosporine-A from poly(D,L-lactide-co-glycolide implants obtained by solvent/extraction evaporation

Cyclosporine-A-loaded PLGA implants were developed intended for ocular route. Implants were prepared using solvent extraction/evaporation technique followed by casting of the cake into rods in a heated surface. XRD patterns showed that cyclosporine-A was completely incorporated into PLGA. FTIR and DSC results indicated alterations on drug molecular conformation aiming to reach the most stable thermodynamic conformation at polymer/drug interface. Implants provided controlled/sustained in vitro release of the drug. During the first 7 weeks, the drug release was controlled by the diffusion of the cyclosporine-A; and between 7-23 week period, the drug diffusion and degradation of PLGA controlled the drug release.

Development and validation of a High Performance Liquid Chromatographic method for determination of etoposide in biodegradable polymeric implants

A method using HPLC-UV was developed and validated for the determination of etoposide incorporated into polycaprolactone implants. The method was carried out in isocratic mode using a C18 column (250 x 4.6 mm; 5 µm), at 25 ºC, with acetonitrile and acetic acid 4% (70:30) as mobile phase, a flow rate of 2 mL/min, and UV detection at 285 nm. The method was linear (r² > 0.99) over the range of 5 to 65 µg/mL, precise (RSD < 5%), accurate (recovery of 98.7%), robust, selective regarding excipient of the sample, and had a quantitation limit equal to 1.76 µg/mL. The validated method can be successfully employed for routine quality control analyses.

Biodegradable nanoparticles obtained from zein as a drug delivery system for terpinen-4-ol

Biodegradable nanoparticles (NPs) have received considerable attention because of their possible use in the development of strategies for the topical delivery of oils and therapeutic drugs, particularly when drug penetration in dermis is desired. Zein is a prolamine and is a promising material for the design of drug delivery systems. In this study, NPs were prepared with zein and were used to encapsulate and release terpinen-4-ol, which is a therapeutic agent for the treatment of melanoma. The results show that the zein NPs are promising nanostructured systems for the prolonged delivery of T4OL with potential applications in anti-melanoma therapy.

Produção e caracterização de polihidroxialcanoatos obtidos por fermentação da glicerina bruta residual do biodiesel

The aim of this study was to evaluate the production of polyhydroxyalkanoates (PHAs) by fermentation of Crude Glycerin, a byproduct of the biodiesel industry, by Cupriavidus necator IPT 026, 027 and 028. The influence of fermentation time and temperature in shake flasks were evaluated. The highest PHA production (2.82 g L-1) occurred at 35 ºC for 72 h of fermentation. The melting and initial thermal degradation temperatures of this PHA were 177.9 ºC and 306.33 ºC, respectively, with 55% crystallinity. FTIR spectrum was similar to those reported in literature. The polymer obtained presented three different methyl esters of hydroxyalkanoates in its composition, with molecular weight of 630 kDa. Bacteria can use Crude Glycerin as an inexpensive substrate to produce value-added biodegradable products, such as PHA.