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Biomedical subjects

M C Tanzi

Publications and source records attributed to M C Tanzi.

31 records · Page 2Linked to original sources

Heparinizable segmented polyurethanes containing poly-amidoamine blocks.

A poly-ether-urea-urethane was synthesized by copolymerization of 4,4'-diphenylmethanediisocyanate (MDI), propanediamine, and poly-oxytetra-methylene glycol (M.W. 1000). Two other corresponding copolymers were also synthesized by adding amino terminated poly-amidoamine macromonomers, purposely synthesized, so as to insert relatively small amounts (6 and 15 weight %) of two types of poly-amidoamine segments in the final product. Of the three copolymers several physicochemical and mechanical properties have been determined, and their heparin adsorption ability, blood compatibility, and cytotoxicity evaluated.

Adsorption↗

New polymeric and oligomeric matrices as drug carriers.

The preparation of polymeric derivatives of drugs, in which drug moieties are covalently linked to polymeric or oligomeric matrices, in such a way that they can be released at the site of action, is one of the most promising ways to achieve results which often can be hardly obtained by other means, such as, for instance, better adsorption by some ways of administration (e.g., oral administration), preferential localization in the body, and longer duration of activity. The aim of this review is to provide an up-to-date picture of the state of art in this field. The synthetic aspects of the preparation of polymeric derivatives of drugs will be discussed, with special emphasis on general methods. The main criteria for selecting a particular type of matrix, and a particular bond between drug and matrix, in order to achieve a given purpose, will be also discussed. The main pharmacological results so far obtained by this technique will be emphasized.

Capsules↗

Heparinizable graft copolymers from chlorosulphonated polyethylene with poly(amido-amine) segments.

The synthesis and the physical characterization of three graft copolymers (PES/PAA) obtained from chlorosulphonated polyethylene (PECS) and three different secondary amino end-capped poly(amido-amine)s are reported. The properties of these heparinizable materials appear to be suitable for constructing prosthetic devices for biomedical use. The heparin adsorbing ability and the stability of the complex with heparin of the three copolymers have been evaluated, by means of biological tests, as activated Partial Thromboplastin Time (PTT) and Thrombin Time (TT).

Adsorption↗

Polyacrylonitrile membranes in hemodialysis: blood-surface interactions.

Investigations of blood-surface interaction phenomena with polyacrylonitrile-based membrane (AN-69) during hemodialysis are reported. The amount and surface distribution of adhering white blood cells (WBC), and adsorbed proteins (Pt) have been evaluated by image analysis of WBC, spectrophotometry and SDS-polyacrylamide gel electrophoresis of desorbed proteins. The protein contents of the patient's serum have been also investigated by SDS-electrophoresis. Results indicate that the distribution of both WBC, and Pt is non-uniform, and higher (71%, and 79% of the total detected amount, respectively) in the half membrane near the blood inlet (PAN-IN); PAN-IN and PAN-OUT eluates show the same protein bands by electrophoresis. The concentration of the proteins stably adsorbed on the membranes appears not to be related to their concentration in the patient's serum. A relatively strong band at MW = 14,400 in PAN eluates could be interpreted as the presence of lysozyme bound to the AN-69 membranes.

Acrylic Resins↗

Fractionation techniques in a hydro-organic environment. II. Acryloyl-morpholine polymers as a matrix for electrophoresis in hydro-organic solvents.

The properties of gels prepared either from acryloyl-morpholine (ACM) or from its mixtures with acrylamide and crosslinked either with bisacrylylpiperazine or with methylenebisacrylamide have been described. ACM-containing gels are compatible with organic solvents. If polymerized in water and dried, they are able to reswell, e.g., in dimethyl sulfoxide or dimethylformamide. If polymerized in presence of dimethylformamide, they form perfectly clear gels, whose mechanical properties are by far superior than those of similar plain polyacrylamide formulations.

Acrylic Resins↗

Synthesis and characterization of poly(amido-amine)s belonging to two different homologous series.

Systematic work on the synthesis and characterization of two series (referred to as type A and B) of poly(amido-amine)s with tertiary amino-groups in the main chain is reported. The polymers were synthesized by polyaddition of alpha, omega-bis-(methyl-amino) alkanes with 1,4-bis-acryloylpiperazine (type A) and 1,12-bis-acryloyl-n-diaminododecane (type B). These materials, which will be employed in the preparation of block and graft copolymers for biomedical use, have been characterized by means of various techniques and the most interesting features are reported.

Adsorption↗

Heparin adsorbing capacities at physiological pH of three poly(amido-amine) resins, and of poly(amido-amine)-surface-grafted glass microspheres.

Three poly(amido-amine)s of similar structure in the form of highly hydrophilic crosslinked resins, have been prepared, and tested for their heparin-adsorbing capacity at physiological pH. They showed different capacities, and their capacities were related to their basicities. One of the same polymers was grafted on the surface of glass microspheres. After treatment, it was shown that the microspheres could adsorb significant amounts of heparin. In all cases most of the adsorbed heparin was hardly eluted with saline, plasma, or blood, but could be recovered by eluting with 0.1 M NaOH. The resins were found to have some haemolytic properties, but no haemolysis was observed with the grafted microspheres.

Adsorption↗

Synthesis and pharmacological evaluation of poly(oxyethylene) derivatives of 4-isobutylphenyl-2-propionic acid (ibuprofen).

The synthesis of three oligomeric derivatives of 4-isobutylphenyl-2-propionic acid (ibuprofen), namely, the monoester of tetraethylene glycol (I) and the diesters of poly(oxyethylene) samples having molecular weights of 1000 (+/- 50) and 2000 (+/- 150) (II and III), has been performed via the imidazolide method. The antiinflammatory activity of I-III, and of equivalent amounts of free drug, was determined in the carrageenan-induced rat paw edema assay at different times after oral administration and found to be considerably prolonged in the case of the three derivatives. The lowest molecular weight derivative (I) also had an enhanced initial activity with regard to 4-isobutylphenyl-2-propionic acid. These results were confirmed by measuring the plasma levels of 4-isobutylphenyl-2-propionic acid in rats at different times after oral administration.

Animals↗

In vivo study of polyurethane-coated Gianturco-Rosch biliary Z-stents.

PURPOSE: Prototypes of Gianturco-Rosch Z-stents coated with polycarbonate urethane (PCU) were placed in the biliary tree of pigs, in order to test their biomechanical behavior, stability, and biocompatibility. METHODS: The stents were surgically implanted in the common bile duct of three pairs of pigs, which were killed after 1, 3, and 6 months respectively. Explanted livers from pigs of the same race, age, and size were used to provide comparative data. The bile ducts were radiologically and histopathologically examined; the stents were processed and examined by scanning electron microscopy. RESULTS: No complications occurred and the animals showed a normal weight gain. The main bile duct appeared radiologically and macroscopically dilated, but the stents proved to be in place. Histologically, the bile duct epithelium was destroyed, but neither hyperplastic nor inflammatory fibrotic reactions of the wall were evident. Both the metallic structure and the polymeric coating of the stents were intact. A layer of organic material with a maximum thickness of approximately 3 micron was evident on the inner surface of the stents. CONCLUSION: The present in vivo study demonstrates the biocompatibility, efficacy, and stability of PCU-coated Gianturco-Rosch stents in the biliary environment.

Animals↗

Linear poly(ethylene oxide)-based polyurethane hydrogels: polyurethane-ureas and polyurethane-amides.

Over the last 30 years, water-swellable and water-insoluble hydrogels have been extensively investigated and developed, leading to a large family of materials which have found uses in a wide range of biomedical applications. While hydrogels usually present a crosslinked structure, linear polyurethane-ureas (PUUs) based on poly(ethylene oxide) have been shown to be able to absorb and swell with aqueous media without dissolving. This behavior is due to the phase separated domain morphology, where hydrogen bonded urethane/urea hard segment domains are dispersed in a PEO soft segment domain. This work investigates the possibility of obtaining linear poly(ethylene oxide)-based polyurethane-amide (PUA) hydrogels using two amide diols as chain extenders, a mono amide diol (AD) and a diamide diol (DD), and a dicarboxylic acid (maleic acid, MA). Poly(ethylene oxide) based PUAs were obtained using a "one-shot" bulk polymerization technique. The chemicophysical characterization and water-solubility tests showed that these materials, while having molecular weights similar to the PUUs, do not possess sufficient phase separation, hydrogen bonding and hydrophobicity of the hard segment domains to exhibit hydrogel behavior. Crosslinked PUAs using maleic acid as chain extender show interesting hydrogel properties.

Journal Article↗

Silk fibroin-polyurethane scaffolds for tissue engineering.

Silk fibroin (SF) is a highly promising protein for its surface and structural properties, associated with a good bio- and hemo-compatibility. However, its mechanical properties and architecture cannot be easily tailored to meet the requirements of specific applications. In this work, SF was used to modify the surface properties of polyurethanes (PUs), thus obtaining 2D and 3D scaffolds for tissue regeneration. PUs were chosen for their well known advantageous properties and versatility; they can be obtained either as 2D (films) or 3D (foams) substrates. Films of a medical-grade poly-carbonate-urethane were prepared by solvent casting; PU foams were purposely designed and prepared with a morphology (porosity and cell size) adequate for cell growth. PU substrates were coated with fibroin by a dipping technique. To stabilize the coating layer, a conformational change of the protein from the alpha-form (water soluble) to the beta-form (not water soluble) was induced. Novel methodology in UV spectroscopy were developed for quantitatively analyzing the SF-concentration in dilute solutions. Pure fibroin was used as standard, as an alternative to the commonly used albumin, allowing real concentration values to be obtained. SF-coatings showed good stability in physiological-like conditions. A treatment with methanol further stabilized the coating. Preliminary results with human fibroblasts indicated that SF coating promote cell adhesion and growth, suggesting that SF-modified PUs appear to be suitable scaffolds for tissue engineering applications.

Journal Article↗

Calcified matrix production by SAOS-2 cells inside a polyurethane porous scaffold, using a perfusion bioreactor.

The repair and regeneration of damaged or resected bone are problematic. Bone autografts show optimal skeletal incorporation, but often bring about complications. Hence, there is increasing interest in designing new biomaterials that could potentially be used in the form of scaffolds as bone substitutes. In this study we used a hydrophobic cross-linked polyurethane in a typical tissue-engineering approach, that is, the seeding and in vitro culturing of cells within a porous scaffold. The polyurethane porous scaffold had an average pore diameter of 624 microm. Using a perfusion bioreactor, we investigated the effect of shear stress on SAOS-2 human osteoblast proliferation and calcified matrix production. The physical, morphological, and compressive properties of the polyurethane foam were characterized. At a scaffold perfusion rate of 3 mL/min, in comparison with static conditions without perfusion, we observed 33% higher cell proliferation; higher secretion of osteopontin, osteocalcin, decorin, and type I collagen (9.16-fold, 71.9-fold, 30.6-fold, and 18.12-fold, respectively); and 10-fold increased calcium deposition. The design of the bioreactor and the design of the polyurethane foam aimed at obtaining cell colonization and calcified matrix deposition. This cultured biomaterial could be used, in clinical applications, as an osteoinductive implant for bone repair.

Biocompatible Materials↗