Novel nanostructured biomaterials for biomedical applications

The research activity reported in this thesis was focused on bottom-up design, production and characterization of biomaterials in the form of medical devices for biomedical applications. More specifically, both a biomaterial for anastomosis after colorectal cancer resection, and a biomaterial for chronic non-healing wounds have been designed and developed, by exploiting the same manufacturing strategy. In the first part of the work, the research has been mainly aimed to obtain a device for preventing the leakage of the anastomosis following surgical treatment of colorectal cancer. The anastomotic leakage is a defect of the intestinal wall at the anastomotic site, which leads to a communication between the intra- and extra-luminal compartments. This study was part of the scientific activity forecasted by the European project AnastomoSEAL (FP7, c.n.280929). The project aim was to develop a patch to be wrapped around the anastomosis, capable to promote the healing of the wound. Specific biomolecules were chosen as biomaterial components. Alginate was selected for its ability to form gels thus providing the physical matrix; Hyaluronic Acid (HA) was chosen for its ability to stimulate wound healing; Butyric acid (But) was chosen since recent data demonstrated its beneficial effect on colorectal anastomosis in animal models. The last two components have been also chemically combined in the Hyaluronic Acid Butyric ester (HABut) molecule. Patches with alginate and HA were produced by using various polymer concentrations, different alginate types (algal sources), and HA with different molecular weights, in order to fine-tune the composition and the performances for the final application. Moreover, in vitro biological tests were performed on the patch components (raw materials): the effects on cell viability, proliferation and extracellular matrix production were studied on primary human fibroblasts and on a normal-derived colonocyte cell line. Additional biological in vitro tests were conducted in order to study more in depth the effect of But on colonocytes. The obtained in vitro data enabled the selection of the best performing formulation and lead to the decision to exclude the use of HABut and But from the medical device. The second part of the work was focused on a biomaterial for chronic non-healing wounds treatment. Chronic non–healing wounds are defined as wounds that do not heal in eight weeks and are characterized by a prolonged inflammation, excess of proteolytic enzymes, reduced cell proliferation and migration, and infections which further sustains these deregulations. For the development of the medical device for chronic non-healing wounds application alginate and HA were also chosen. Moreover, silver nanoparticles (nAgs) were added for their antibacterial and anti-inflammatory activity, and for their ability to inhibit proteolytic enzymes. nAgs are produced in wet conditions from silver nitrate and reducing compounds in the presence of the biopolymer Chitlac as dispersion agent. A foamed biomaterial was prepared in order to increase the ratio surface/volume and therefore to enhance the bacterial exposure to nAg. The foam has been obtained by using hydroxy-methyl-2-propyl cellulose (HPMC), a cellulose water soluble derivative already employed for this purpose in many biomedical and pharmaceutical applications. The HPMC-foamed patch was characterized by structural, mechanical and biological analysis: scanning electron microscopy (SEM) and tensile strength measurement were performed. The overall data confirmed that the biomaterial obtained is a promising material for the chronic non-healing wound application.