A Nerve Cell Growth Promoting PEG-Peptide Block Copolymer and Photoresponsive Hydrogels with Tailorable Mechanical Properties and Feasible Degradability

In this study, a novel photoresponsive poly-(ethylene glycol)-peptide (PEG-peptide) diblock copolymer capable of promoting pheochromocytoma cell (PC12) growth is developed, and the corresponding hydrogels with tunable mechanical properties for nerve tissue engineering are constructed via bridge-micelle architectures. The PEG-peptide forms core-shell micelles in the precursor solution, in which the core peptide segment contains γ-benzyl-l-glutamate moieties to stimulate nerve cell growth and coumarin moieties to provide photoresponsivity, while the hydrophilic PEG shell could enhance stable dispersion of micelles. Meanwhile, coumarin-containing water-soluble random copolymers poly-(<i>N</i>,<i>N</i>-dimethylacrylamide-random-acrylic-(7-(2-acryloyloxyethoxy)-4-methylcoumarin)) (PDA) are incorporated to function as bridges. The coumarin moieties in both polymers undergo [2 + 2] cycloaddition upon 365 nm UV irradiation, resulting in the coexistence of three different types of cross-linking: intramicelle, micelle-bridge, and interbridge cross-linking. By adjusting the composition and concentration of the precursor solutions as well as 365 nm UV irradiation time to delicately balance these cross-linkings, hydrogels with a wide range of mechanical strengths, swelling ratios, and viscoelastic behaviors are feasibly fabricated. This construction not only expands the gelation window but also exerts an effective approach to precisely modulate mechanical properties and water absorption of hydrogels, which could further optimize the environment for cell growth. The complex modulus of the hydrogels is tunable between 238 and 1448 Pa, aligned with the mechanical strength of native extracellular matrix for PC12 cell growth. It is noteworthy that a high complex modulus and high swelling ratio could be concurrently achieved, enabling excellent PC12 cell growth performance in cell cytotoxicity and 3.2 times cell viability with respect to the control group. Additionally, upon 30 min of 254 nm UV irradiation, the hydrogels can be un-cross-linked into solutions via dedimerization of coumarin, offering a great potential for clean scaffold removal. These achievements demonstrate that the hydrogel system provides a cytocompatible and supportive biochemical environment, offering promising potential as a foundational platform for nerve-regeneration scaffold design.