The self-healing mechanism and bioelectrochemical interface properties of supramolecular gels have been rarely explored. In this context, we propose a constitutive "fibril-reorganization" model to reveal the self-healing mechanism of a series of core-shell structured guanosine-borate (GB) hydrogels and emphasize that interfibrillar interactions at the supramolecular polymer scale (G-quadruplex nanowires) drive the self-healing process of GB hydrogels. Structure-electrochemical sensing performance studies reveal that GB hydrogel nanofibers with relatively strong biomolecular affinity such as -SH modified GB hydrogel (GB-SH) show a high sensitivity of response and low limit of detection for tumour marker alpha-fetoprotein sensing (AFP; 0.076 pg mL(-)(1)). Guanosine/ferroceneboronic acid (GB-Fc) hydrogel nanofibers with superior conductivity and redox activity display the widest linear detection range for AFP (0. 0005-100 ng mL(-1)). Structure-property correlations of GB hydrogels provide useful insight for the future design of advanced self-healing materials and electrochemical biosensors. (C) 2021 Elsevier Inc. All rights reserved.