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In this work, a novel enzymatically crosslinked injectable hydrogel comprising hyaluronic acid (HyA), dopamine (DA), and 3-(4-Hydroxyphenyl) propionic acid (HPA) conjugates was successfully developed. To the best of our knowledge, it is the first time that HPA is conjugated to a HyA-based backbone. In situ hydrogelation of HyA-DA-HPA occurred in the presence of hydrogen peroxide (H2O2) as an oxidant and horseradish peroxidase (HRP) as a catalyst. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to characterize the chemical reactions between HyA, DA, and HPA. Gel formation completed between 3 s to 5 min depending on the concentrations of polymer, HRP, and H2O2. Crosslinked HyA-DA-HPA gels acquired storage moduli ranging from ~100 Pa to ~20000 Pa (at f = 2000 rad/s). Biocompatibility of the hydrogels was examined with human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cell-derived neural stem cells. The hydrogels made of 2.0 w/v % HyA-DA-HPA hydrogels, 0.24 U/mL HRP and ≤ 0.5 µmol/mL H2O2 were found biocompatible with hMSCs cultured on and encapsulated within the hydrogels. Since HyA serves as a backbone of the extracellular matrix in the central nervous system (CNS) and DA acquires the ability to restore dopaminergic neurons, use of this injectable HyA-DA-HPA hydrogel for stem cell transplantation is a potential treatment strategy for CNS repair and regeneration.

Original publication




Journal article


Biomedical materials (Bristol, England)

Publication Date



Biomaterials and Tissue Engineering, University College London, London, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.