Mechanically-reinforced biocompatible hydrogels based on poly (N-isopropylacrylamide) and star-shaped polycaprolactones

The aim of this work was to improve the properties of hydrogels based on poly(N-isopropyl acrylamide) (PNIPAAm) in terms of mechanical features and functionality by combining the polymer with a star-shaped tetrafunctional polycaprolactone (PCL), which was synthesized ad-hoc and introduced into the reaction mixture. The synthesized PCL (coded as PCL-COOH), selected to maintain the biocompatibility of the final material, was designed with a star structure characterized by four strong arms ending with maleic groups to increase the functionalization potential capable of participating in the radical polymerization and adding acid groups to the system. Specifically, various hydrogels were prepared by partially replacing pentaerytritol tetraacrylate (PE-TA), a commercial crosslinker, with increasing concentrations of PCL-COOH in the presence of trihexyl(tetradecyl) phosphonium persulfate (TETDPPS) as non-gas-releasing radical initiator. In addition, frontal polymerization (FP) was employed, a fast and energy efficient technique, potentially capable of promoting the dispersibility of PCL in the polymer matrix. The influence of the star-shaped PCL on the polymerization process as well as on the hydrogel properties in terms of chemical structure, swelling behaviour, thermal and mechanical features was investigated. Indeed, it was found that the presence of PCL allowed the formation of a stable polymerization front up to a concentration of 25 wt%. FT-IR measurements allowed to evaluate the fraction of PCL effectively bonded to the hydrogel structure, while the morphological analysis performed by FE-SEM characterization revealed that the hydrogel pore size tended to decrease as the amount of PCL in the system increased. In addition, the star-shaped PCL was found to affect the material swelling properties, by reducing the swelling ratio without affecting the thermoresponsive behavior. Mechanical tests performed on the neat PNIPAAm hydrogels and on PCL-containing hydrogels, showed a relevant increase in the material stiffness due to the PCL-COOH addition. The DSC characterization results showed a decrease in the glass transition temperature with increasing PCL-COOH content, indicating a partial miscibility of the two polymers likely due to a compatibilization effect of a copolymer formed during the polymerization process. To demonstrate the capability of the hydrogels to retain positively charged molecules, the prepared systems were contacted with solutions containing pararosaniline hydrochloride. The retention capacity as well as the kinetic release were investigated. The measurements evidenced a higher retaining capacity and a lower release rate in the PCL-containing hydrogels. Finally, the biocompatibility and the low citoxicity of the PNIPAAm/PCL hydrogels were confirmed by a cell viability assay using the SH-SY5Y cell line.