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

TL;DR

A new hydrogel system is developed that supports nerve cell growth and can be tailored for mechanical properties and degradation.

Contribution

A novel PEG-peptide copolymer and photoresponsive hydrogel system with tunable mechanical properties and feasible degradability is introduced.

Findings

The hydrogel system supports PC12 cell growth with 3.2 times higher cell viability compared to the control group.

The complex modulus of the hydrogels can be tuned between 238 and 1448 Pa, matching native extracellular matrix properties.

The hydrogels can be degraded via 254 nm UV irradiation, enabling clean scaffold removal.

Abstract

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(N,N-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.

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