Luigi Lazzeri

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.

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.

Hydrogels of poly(vinyl alcohol) and collagen as new bioartificial materials Part I Physical and morphological characterization

Poly(vinyl alcohol) was used to make hydrogels containing various amounts of collagen. These “bioartificial materials”, made of synthetic and biological polymers, were studied to investigate the effect of the presence of the collagen on the structural properties of the hydrogels. A comparison between thermal and morphological properties of collagen-containing hydrogels and hydrogels of pure poly(vinyl alcohol) was made.

Poly(vinyl alcohol) hydrogels as hydrophilic matrices for the release of lipophilic drugs loaded in PLGA nanoparticles.

Poly(vinyl alcohol) (PVA) hydrogels prepared by a freeze-thawing procedure were evaluated as matrices for the release of water-insoluble drugs such as dexamethasone. As it is impossible to directly entrap a lipophilic drug into a hydrophilic matrix, a novel mechanism has been designed based on producing biodegradable nanoparticles loaded with the drug, that could then be entrapped into the hydrogels. Nanoparticles were prepared by a solvent evaporation technique using a biodegradable copolymer of poly(lactic acid)-poly(glycolic acid) (PLGA). The effects of several processing parameters on particle properties were investigated. The drug release from free nanoparticles was compared to that from the nanoparticles entrapped into the PVA matrices. It was observed that the release profile of the drug is not significantly affected by the PVA matrix. A correlation was found between the amount of drug released and the PVA concentration in the hydrogels: the percentage of drug released, as a function of time, decreased by increasing PVA concentration, indicating that PVA concentration can be used as a tool in modulating the release of the drug.

Physico-chemical and mechanical characterization of hydrogels of poly (vinyl alcohol) and hyaluronic acid

Hydrogels are three-dimensional polymeric networks very similar to biological tissues and potentially useful as soft tissue substitutes and drug delivery systems. Many synthetic polymers can be used to make hydrogels: poly (vinyl alcohol) is widely employed to make hydrogels for biomedical applications. Improvements in the biocompatibility characteristics of synthetic materials could be achieved by the addition of biological macromolecules. The resulting materials named “bioartificial polymeric materials” could possess the good mechanical properties of the synthetic component and adequate biocompatibility due to the biological component. We have used poly (vinyl alcohol) to make hydrogels containing various amounts of hyaluronic acid. These bioartificial materials were studied to investigate the effect of the presence of the hyaluronic acid on the structural properties of the hydrogels. Thermal, mechanical, morphological and X-ray analyses were performed. A close correspondence between the network consistency and the degree of crystallinity developed in the matrix suggested that the hyaluronic acid, when its content is about 20%, could provide heterogeneous crystallization nuclei for poly (vinyl alcohol) thus increasing the crystallization degree, and consequently, the storage modulus.

Dextran/Poly(acrylic acid) Mixtures as Miscible Blends

Bioartificial polymeric materials based on blends of dextran and poly- (acrylic acid) were prepared in form of films and characterized in order to evaluate the miscibility of the natural component with the synthetic one. Films with different composition ratios were prepared by solution casting and analyzed by dynamic mechan- ical-thermal analysis, differential scanning calorimetry, and scanning electron micros- copy. The obtained results indicate that dextran is miscible with poly(acrylic acid). The miscibility was mainly ascertained on the bases of the occurrence of a single composition-dependent glass transition temperature in each blend and also on the bases of the transparency and homogeneity of the films. q 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 2089-2094, 1997

Bioartificial materials based on collagen: 1. Collagen cross-linking with gaseous glutaraldehyde

The effect of exposure time of thin films of soluble collagen to glutaraldehyde (GTA) vapour was studied at 37 degrees C, and was evaluated by examining the thermal and biological stability and the swelling ratio. It was found that the collagen films treated with GTA vapour for 18 h showed the highest denaturation temperature, the lowest swelling ratio, and an enhanced proteolytic stability. This study shows that soluble collagen can be effectively cross-linked with GTA vapour and that the degree of cross-linking can be controlled by varying the exposure time.