Thermo-responsive injectable hydrogels from linear and star-shaped block copolymers composed of amino acid-derived vinyl polymer and poly(ethylene glycol) for biomedical applications

Abstract

Injectable hydrogels possess great potential in industrial, biomedical, and cosmetic applications. This study presents the synthesis and characterization of novel thermo-responsive injectable hydrogels derived from amino acid-derived vinyl polymer/polyethylene glycol (PEG) hybrid block copolymers. Two types of block copolymers, linear (1n, n = 101, 250, 321: chain length of amino acid-based polymer block) and star-shaped (tetra-branched 2n, n = 28, 66, 118), were successfully prepared via atom transfer radical polymerization of N-acryloyl-L-alanine methyl ester (NAAMe) using PEG macroinitiators, and their gelation behaviors were comprehensively explored. In a dilute aqueous solution (1 wt%), both linear and star polymers exhibited lower critical solution temperature behavior, with a transition temperature (T_t) of 20 °C. At higher polymer concentrations, hydrogels are formed for all polymers at temperatures above T_t, with star-shaped copolymers exhibiting significantly better gelation ability (minimum gelation concentration: 6 wt% (2₁₁₈) and 17 wt% (1₃₂₁)). These block copolymers respond rapidly to temperature changes, facilitating instant gelation at body temperature through self-assembly, thus making them sophisticated injectable hydrogels. Structural factors, such as PNAAMe length and polymer shape, influence their self-assembled structure, including network density, enabling tunable mechanical properties of the gels. Furthermore, these block copolymers demonstrated good cytocompatibility and negligible macrophage activation. Thus, the PNAAMe/PEG block copolymers serve as efficient injectable three-dimensional-scaffolds for tissue engineering and controlled release.