Sintesi di biomateriali con design molecolare "ad hoc" per applicazioni biomedicali: dal rilascio controllato di farmaci all'ingegneria tissutale

The aim of the research work was the synthesis and characterization of new A-B-A triblock copolymers of polylactic acid (PLLA), whose chemical structure was ad hoc designed for the preparation of: micro- and nanoparticles for controlled drug delivery; polymer film with elastomeric properties for soft tissue engineering application. The A block consists of PLLA, while the B block (previously synthesized by the research group of Prof. Lotti, co-supervisor of this work) is an equimolar copolymeric system poly(butylene/triethylene succinate) with different sequences length: block copolymer (long sequences of both co-units)and random copolymer (very short sequences of both co-units)The random B block was also used for the realization of a high molecular weight A-B-A triblock copolymer, obtained by chain extending the low molecular weight A-B-A triblock. The different molecular architecture proved to be an effective tool in modulating the hydrophilicity, the crystallinity degree and the kinetics of the hydrolytic degradation of the final material. The results indicate that it is possible to modulate the release kinetics by acting both on the architecture of the B block and on the size of the particles. Furthermore, the mechanical properties of the high molecular weight A-B-A triblock copolymer are significantly improved with respect to those of the homopolymer, making the material a very interesting candidate for soft tissue engineering: the elastic modulus is reduced by two orders of magnitude, and the elongation at break increases from 2 to 100%. Regarding the kinetics of the hydrolytic resorption, the findings show the rate of degradation is slowed down by copolymerization. Lastly, it is worth mentioning the improvement by copolymerization of the thermal stability (important parameter for the processability of a biomaterial) of PLLA.