Добірка наукової літератури з теми "Polycatecholamines"

Curdlan (β-1,3-glucan), as a biodegradable polymer, is still an underestimated but potentially attractive matrix for the production of dressing materials. However, due to its lack of susceptibility to functionalization, its use is limited. The proposed curdlan modification, using a functional polycatecholamine layer, enables the immobilization of selected oxidoreductases (laccase and peroxidase) on curdlan hydrogel. The following significant changes of biological and mechanical properties of polycatecholamines + oxidoreductases-modified matrices were observed: reduced response of human monocytes in contact with the hydrogels, modulated reaction of human blood, in terms of hemolysis and clot formation, and changed mechanical properties. The lack of toxicity towards human fibroblasts and the suppression of cytokines released by human monocytes in comparison to pristine curdlan hydrogel, seems to make the application of such modifications attractive for biomedical purposes. The obtained results could also be useful for construction of a wide range of biomaterials based on other polymer hydrogels.

Collagen-sealed polyester (PET) prostheses are commonly used in reconstructive vascular surgery due to their self-sealing properties. To prevent post-surgical infection, different modification methods have been tested but so far none have showed long-term satisfactory efficiency. For this reason, in the present study, a commercial collagen-sealed PET prosthesis was coated by a highly adhesive poly (L-DOPA) layer maintaining the sealing protein without losing the original properties and functionality. This modified (as proven by SEM, FTIR, XPS and contact angle) graft exhibited comparable wettability and elasticity as pristine commercial graft, as well as reduced hemolysis-inducing effect, lowered toxicity against human endothelial cells and reduced toxicity in Danio rerio model. Poly (L-DOPA)-coated grafts were shown to bind six times more aminoglycoside antibiotic (gentamicin) than pristine graft. Poly (L-DOPA)-coated antibiotic-bound prostheses exhibited an improved antibacterial activity (bacterial growth inhibition and anti-adhesive capacity) in comparison with pristine antibiotic-bound graft. Overall, poly (L-DOPA)-coatings deposited on PET vascular grafts can effectively functionalize collagen-sealed prostheses without the loss of protein sealing layer and allow for antibiotics incorporation to provide higher safety in biomedical applications.

This dissertation primarily focuses on biomimicry, the term coming from the Greek words bios meaning life in Greek and mimesis meaning to imitate, a field that seeks to mimic natural mechanisms, structures, and functions to exploit them into several scientific applications. We have been exploring nature-inspired catecholamine-based biopolymers to straightforwardly develop molecularly imprinted polymers (MIPs), mimetic receptors, for bioanalytical and diagnostics applications. From a more comprehensive standpoint, this dissertation addressed the broad need for simple, cost- effective, and accurate catecholamine-based assays, using animal-free reagents. The general structure of this dissertation is explained herein along with an overview of the research goals. Chapter 1 is devoted to the description of MIPs design and to how they are synthesized. The Chapter gives a brief outline of molecular imprinting technology (MIT) along with recent MIPs synthesis progresses, focusing on the selection of the template molecule, a critical factor to assemble efficient receptor mimics. Chapter 2 deals with catechol-derived biopolymers, chiefly focusing on polydopamine (PDA) and polynorepinephrine (PNE), which are becoming increasingly appreciated as soft, sustainable, versatile, and biocompatible materials able to address challenging tasks. Chapter 3 reports on the use of MIPs for the detection of the small peptide, namely gonadorelin, in biological specimens, i.e., human urines. This is the main purpose of the PhD research study which is part of a larger project entitled “New analytical approaches aimed at tackling doping in sports: development of optical biosensors for the analysis of peptide hormones through molecularly imprinted polymers” funded by the Italian Ministry of Health. First, an optical, label-free, and real time sensing strategy was developed for the detection of gonadorelin using Surface Plasmon Resonance (SPR) transduction. In addition, a portable test was settled, motivated by the lack of decentralized rapid gonadorelin assays for quick decision-making and extensive athlete monitoring before and during competitions. More in detail, a biomimetic enzyme-linked immunosorbent assay (BELISA) was developed onto disposable microplates aiming to cut testing costs and time that are usually required for gonadorelin detection (e.g., mass spectrometry). The detection of gonadorelin through a MIP-based bioanalytical approach has been a very ambitious goal, as no point-of-care devices and only a few monoclonal antibodies are commercialized targeting this analyte. The MIP based approach is able to cheaply measure the drug levels directly from human urine specimens by using a small sample volume (in order of microliters). More specifically, a polynorepinephrine (PNE) based MIP was first designed for targeting gonadorelin, and then it was employed as a receptor element in an SPR-based optical sensing platform. A competitive bioanalytical label-free assay has been built over the MIP for gonadorelin quantification in urine samples. After this, the second task of the project involved the scaling down of the competitive assay, i.e., BELISA, into a portable and simple platform to analyze human urine. The strategy developed was validated by mass spectrometric analysis. Urine samples and LC-MS/MS equipment were available at Pisa University Hospital’s Clinical Pathology Lab, partner of the project. Very soon, the journey across MIPs will continue in the direction of nano- MIPs, which we foresee could be further used as advantageous alternatives to antibodies, both in vitro diagnostics and in vivo therapeutic applications. Chapter 4 is, thus, about the preliminary development of catecholamine- based nanoparticles which will be implemented in the MIPs nanotechnological applications. Chapter 5 describes how catecholamines may be exploited in colorimetric microplate-based bioassays to screen different analytes, in addition to their use as functional monomers in mimetics (MIPs) synthesis. In this case, the redox PDA properties, and the capability to build up coating, non-imprinted material, were exploited for analytical purposes. Two colorimetric tests for molecular diagnostics were developed and applied respectively to analyze serum albumin, a biomarker for kidney function, in human fluids (urine) and to preliminarily screen hypochlorous acid, a key determinant for neurodegenerative disorders. Chapter 6 summarizes the pithiest points of the PhD research studies, discussed in the preceding chapters, and introduces considerations for future work on the topic.