Synthesis, characterization and biomimetic functionalization of thermoplastic poly(ester urethane)s

The design of biomaterials has seen a great increase in recent decades, with the specific aim to overcome the inadequacy of traditional materials in addressing the complexity of therapeutic approaches typical of tissue engineering (TE). Polymeric materials, in particular, are undergoing a significant growth in their use as biomaterials for multiple applications. Indeed, compared to metals and ceramics, polymeric biomaterials present many advantages, that include biocompatibility, biodegradability, good mechanical and physical properties and general resistance to common sterilization methods. Moreover, synthetic polymers and especially poly(urethane)s can be ad-hoc engineered enabling the tuning of their characteristics to fit specific applications, which requirements could not be otherwise met. In this work, new poly(ester urethane)s, (PUs), based on poly(ε-caprolactone), 1,6-hexamethylene diisocyanate and linear aliphatic chain extenders (i.e., 1,4-butanediol, 1,8-octanediol, 1,12-dodecanediol) have been designed and characterized to investigate the effects of the different chain length of the chain extender on PU physico-chemical properties. Then, surface modification through plasma treatment in the presence of acrylic acid vapor was investigated to expose carboxyl groups then exploited to graft biomolecules such as gelatin. PU chemical characterization was carried out using Infrared (IR) spectroscopy and Size Exclusion Chromatography (SEC). Mechanical and thermal properties were assessed by tensile tests and Differential Scanning Calorimetry, respectively. PU hydrolytic and enzymatic degradation was also evaluated. Surface modification was performed by plasma treatment in the presence of Ar and acrylic acid vapor. -COOH exposure was evaluated through contact angle measurements and Toluidine Blue O colorimetric assay. The subsequent covalent grafting of a hydrophobic model molecule (i.e., benzylamine) and gelatin was performed exploiting carbodiimide chemistry and studied through IR and 1H Nuclear Magnetic Resonance spectroscopies and colorimetric methods. PU synthesis success was confirmed by IR spectroscopy and SEC. The use of the three chain extenders resulted in significantly different mechanical, thermal and degradation properties on the final PUs. In detail, the chain length of the chain extender turned out to affect the capability of hard segments to crystallize as well as PU resistance to applied tensile strength and enzyme-catalyzed hydrolysis. Plasma treatment resulted in the exposure of a great number of carboxyl groups (10^16 units/cm^2) and a significant increase in wettability (contact angle decrease of 30-40%). Gelatin was also successfully grafted on film surfaces, as demonstrated by IR spectroscopy; conversely, a correct quantification of benzylamine was impaired by hydrophobic absorption phenomena occurring on the surface of control samples. In conclusion, all the designed PUs turned out to be suitable to produce TE scaffolds, with a target on long term applications and hard tissues, also using rapid prototyping techniques such as Fused Deposition Modeling. Moreover, the feasibility to easily surface functionalize them with biomolecules opens the way towards an improvement in the biocompatibility and bioactivity of PU scaffolds. Indeed, the versatility of the carbodiimide chemistry can be exploited to graft the most suitable biological cues (e.g., proteins, amino acids, peptides) for the targeted application.