Biomedical gels: structure and properties

Biomedical hydrogels are defined as biocompatible solid-liquid systems in which polymeric chains (fibers) are crosslinked to form a 3D-network swollen by a huge water amount. Their use as controlled drug release systems is in continuous growth. However, a critical step in their development is the characterization of their 3D nano/micro structure and the correlation with fabrication parameters. Indeed, hydrogels structure is complex and depends on fibers diameter, concentration, mesh/pore size and degree of crosslinking. Historically, hydrogel structure have been imaged using AFM, SEM, TEM and X-ray microscopy. Although these methods provide high-resolution images, they require a significant sample manipulation that can lead to shrinkage and collapse of the fibers structure. Moreover, information is strictly localized and poorly suited for bulk properties. The target of this thesis is to propose the combined use of not-destructive, economic and fast technologies like rheology and low field NMR (LF-NMR) to understand the macro-, micro- and nanoscopic characteristic of several hydrogels. We aim to drastically reduce the need for time-consuming, expensive measurement, rather to select optimal sample for more complex characterization. Reliability of rheological and LF NMR approach were tested to: • follow hydrogel gelation process in i) a sonicated nanocellulose solution ii) a thermo-sensitive chitosan gel. In particular, the effect of i) salt addition and sonicated time and ii) temperature on the gelation process were considered, respectively. • interpret the characteristics of cross-linked gels system relaying on polymer blends [PVP (poly-vinyl-pirrolidone) and alginate]. In particular gels mechanical strength, 3D nano/micro structure and mesh size distribution were determined. Some of these systems, suitable for liposomes delivery, were also characterized by TEM and this technique confirmed our findings. • correlate mesh size and release rate in a Diels-Alder poly(ethylene glycol) based hydrogel for controlled antibodies release. Our estimations well fitted with test of in vitro release of fluorescein isothiocyanate labeled Dextran and Bertuzimab. For what concerns biological tissues, the focus is on two innovative applications of LF-NMR relying on the different conditions experienced by water confined in three-dimensional structures. Indeed, from the LF-NMR point of view, we can distinguish between free water that is not affected by the solid surface, and bound water that undergoes the effect of solid surface: • The first application considers the analysis on the expectorate of patients affected by cystic fibrosis (CF). This pulmonary disease is mainly characterized by a dehydrated and hyper concentrated mucus in airways. We analysed these voluntary samples to reveal mucus dehydration and pathological components, which are strictly correlated to disease severity. As this approach is less expensive, faster, non-invasive and does not require highly qualified personnel, it has the potential to become a valuable monitoring tool. • The second application regards the evaluation of trabecular bone extracts from osteoporosis and osteoarthrosis patients who underwent hip replacement. These two pathological conditions differ for the quality of bone tissue, and both of them are typical of elders. Water mobility inside the trabecular network is connected to the pore size distribution characterising the bone tissue. Therefore we expected that osteoporosis samples present higher water mobility than osteoarthrosis ones. It could be a new method to rapidly and easily know the severity of osteoporosis.