Maria Grazia Cascone

Blends of synthetic and natural polymers as drug delivery systems for growth hormone

In order to overcome the biological deficiencies of synthetic polymers and to enhance the mechanical characteristics of natural polymers, two synthetic polymers, poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) were blended, in different ratios, with two biological polymers, collagen (C) and hyaluronic acid (HA). These blends were used to prepare films, sponges and hydrogels which were loaded with growth hormone (GH) to investigate their potential use as drug delivery systems. The GH release was monitored in vitro using a specific enzyme-linked immunosorbent assay. The results show that GH can be released from HA/PAA sponges and from HA/PVA and C/PVA hydrogels. The initial GH concentration used for sample loading affected the total quantity of GH released but not the pattern of release. The rate and quantity of GH released was significantly dependent on the HA or C content of the polymers.

Bioartificial polymeric materials based on polysaccharides

Bioartificial polymeric materials, based on blends of polysaccharides with synthetic polymers such as poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA), were prepared as films or hydrogels. The physico-chemical, mechanical, and biological properties of these materials were investigated by different techniques such as differential scanning calorimetry, dynamic mechanical thermal analysis, scanning electron microscopy, and in vitro release tests, with the aim of evaluating the miscibility of the polymer blends and to establish their potential applications. The results indicate that while dextran is perfectly miscible with PAA, dextran/PVA, chitosan/PVA, starch/PVA, and gellan/PVAblends behave mainly as two-phase systems, although interactions can occur between the components. Cross-linked starch/PVAfilms could be employed as dialysis membranes: they showed transport properties comparable to, and in some cases better than, those of currently used commercial membranes. Hydrogels based on dextran/PVA and chitosan/PVA blends could find applications as delivery systems. They appeared able to release physiological amounts of human growth hormone, offering the possibility to modulate the release of the drug by varying the content of the biological component.

Gelatin nanoparticles produced by a simple W/O emulsion as delivery system for methotrexate

Biodegradable hydrophilic gelatin nanoparticles, containing different initial amounts of methotrexate (MTX), were prepared using a simple solvent evaporation technique based on a single water-in-oil emulsion and stabilized by the use of glutaraldehyde as cross-linking agent. The effects of several parameters on particle size, drug encapsulation efficiency and drug release were investigated. Size and shape of the nanoparticles were examined by scanning electron microscopy. The release of MTX was monitored in vitro and the mechanism of release was studied. Particles with a mean diameter of 100–200 nm were produced, which were able to release MTX following a diffusion-controlled mechanism of release. It was observed that the initial amount of MTX used for sample loading did not have any effect on the pattern of release, while it affected the amount of drug entrapped into the nanoparticles and also both the release rate and the total amount of drug released.

Collagen-based new bioartificial polymeric materials

Bioartificial polymeric materials, based on blends of biological and synthetic polymers, have been proposed as new materials for applications in the biomedical field. They should usefully combine the biocompatibility of the biological component with the physical and mechanical properties of the synthetic component. Blends of collagen with either poly(vinyl alcohol) or poly(acrylic acid) have been prepared by mixing aqueous solutions of the two polymers. Differential scanning calorimetry and dynamic mechanical thermal analysis has been carried out to investigate the miscibility properties of the polymers and the mechanical behaviour of the blends.

Effect of chitosan and dextran on the properties of poly(vinyl alcohol) hydrogels

Hydrogels are three-dimensional polymeric networks very similar to biological tissues and potentially useful as drug delivery systems. Poly(vinyl alcohol)-based hydrogels containing different amounts of dextran or chitosan were prepared using the freezing–thawing method. Repeated freezing–thawing cycles of a poly(vinyl alcohol) (PVA) aqueous solution lead to the formation of crystallites which act as cross-linking sites, and a hydrogel with a high capacity to swell is obtained. The effects of the two different polysaccharides on the properties of the obtained materials were investigated by differential scanning calorimetry, dynamic mechanical analysis and scanning electron microscopy. In addition the release with time of poly(vinyl alcohol) in aqueous medium, was monitored and evaluated. On the basis of the obtained results it seems that the presence of dextran favors the crystallization process of PVA, allowing the formation of a more ordered and homogeneous structure. Instead, chitosan seems to perturb the formation of PVA crystallites leading to a material with a less regular structure.

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

Block copolymers of L-lactide and poly(ethylene glycol) for biomedical applications

Poly (L-lactide)-poly (oxyethylene)-poly (L-lactide) block copolymers obtained in bulk, by a ring opening mechanism, from poly (ethylene glycol)s (PEG)s and L-lactide (LA), at 120–140°C, in the absence of added catalysts are described. By using PEGs with different molecular masses, 3000 and 35000, respectively, and varying the initial molar ratio LA to PEG, two series of copolymers with different molecular masses, relative length of blocks and hydrophilicity were obtained. Physico-chemical characterization of the copolymers had been previously performed. The morphological characteristics of the copolymers were investigated by means of X-ray diffractometry, optical and scanning electron microscopy. The biological properties of the materials were determined by evaluating their cytotoxicity, cytocompatibility, hemocompatibility and degradability using different standard tests. The results obtained indicate that the block copolymers synthesized may be useful for biomedical applications, in particular as resorbable drug vehicles. The materials are brittle and their mechanical properties are not appropriate for implant devices.

Poly(ester-ether-ester) block copolymers as biomaterials

Poly(ester-ether-ester) block copolymers, belonging to a class of biodegradable materials, were synthesized from poly(ethylene glycol) and ε-caprolactone by a simple ring-opening mechanism, which avoids the use of potentially toxic inorganic or organometallic initiators. The morphological and mechanical properties of such materials were investigated by gelpermeation chromatography, vapour pressure osmometry, proton magnetic resonance, infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry and stress-strain tensile tests. The biocompatibility was investigated by cytotoxicity and hemocompatibility tests; the cytotoxicity was tested by the Neutral Red uptake assay, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, the Kenacid Blue R-binding method, and by the cell proliferation test on polymer films; the hemocompatibility was tested by the contact activation both of the coagulation cascade (intrinsic pathway), by the plasma prekallikrein activation test, and of the thrombocytes, by measuring the release of platelet factor 4 and β-thromboglobulin. The experimental results show that such a polymerization process permits high-molecular mass block copolymers with relatively good tensile and mechanical properties to be obtained. Their cyto- and hemo-compatibility makes them suitable for employment as biomaterials.

Bioartificial materials based on blends of collagen and poly(acrylic acid)

The interactions between soluble collagen (C) from calf skin and poly(acrylic acid) (PAA) were studied. Mixing aqueous solutions of collagen and PAA, at various pH values (2.5-4), leads to the formation of complexes that precipitate in the form of insoluble aggregates. The effects of mixture composition, pH, and ionic strength on C/PAA complex formation were investigated by gravimetric, turbidimetric, and conductometric analysis. The experimental results indicate that the complexes form through electrostatic interactions. Homogeneous solid films with variable C/PAA ratios were obtained by casting from solutions in which the pH was adjusted just over the isoelectric point of collagen, thus avoiding the attractive ionic interactions responsible for the complexation of collagen and PAA molecules. A relevant result obtained is related to the possibility of restoring the ionic interactions between the two polymers inside the solid films. Mixture composition and pH appear to influence the thermal properties of both complexes and films.

Morpho-functional characterization of human mesenchymal stem cells from umbilical cord blood for potential uses in regenerative medicine

Mesenchymal stem cells (MSCs) represent a promising source of progenitor cells having the potential to repair and to regenerate diseased or damaged skeletal tissues. Bone marrow (BM) has been the first source reported to contain MSCs. However, BM-derived cells are not always acceptable, due to the highly invasive drawing and the decline in MSC number and differentiative capability with increasing age. Human umbilical cord blood (UCB), obtainable by donation with a noninvasive method, has been introduced as an alternative source of MSCs. Here human UCB-derived MSCs isolation and morpho-functional characterization are reported. Human UCB-derived mononuclear cells, obtained by negative immunoselection, exhibited either an osteoclast-like or a mesenchymal-like phenotype. However, we were able to obtain homogeneous populations of MSCs that displayed a fibroblast-like morphology, expressed mesenchym-related antigens and showed differentiative capacities along osteoblastic and early chondroblastic lineages. Furthermore, this study is one among a few papers investigating human UCB-derived MSC growth and differentiation on three-dimensional scaffolds focusing on their potential applications in regenerative medicine and tissue engineering. UCB-derived MSCs were proved to grow on biodegradable microfiber meshes; additionally, they were able to differentiate toward mature osteoblasts when cultured inside human plasma clots, suggesting their potential application in orthopedic surgery.