Astrocyte-Guided Maturation of Neural Constructs in a Modular Biosynthetic Hydrogel for Biohybrid Neurotechnologies

Abstract

Bionic implants are increasingly used to restore neural function yet achieving a chronically stable neural interface remains challenging. Biohybrid neurotechnologies aim to overcome this limitation by integrating living tissue components that can promote long-term performance and functional integration with the nervous system. However, existing biomaterial coatings often lack the physiological complexity, cellular heterogeneity, and neurotrophic support required to sustain neural network formation. Here, we present a modular strategy which leverages astrocyte-guided mechanisms of neural network development. A biosynthetic hydrogel was developed using norbornene-functionalized poly(vinyl alcohol) and gelatin (PVA-GEL), crosslinked via visible light-triggered thiol-ene chemistry, to yield bioactive and highly tuneable scaffolds. A systematic characterization varying gelatin content and polymer weight enabled the identification an optimal formulation to promote astrocytic growth, while maintaining mechanical stability and degradation profiles that are compatible with brain implants. Co-encapsulation with neural progenitors promoted neuronal differentiation, neurite outgrowth, and the formation of synaptically competent networks. The construct developed into functional interfaces when in contact with brain tissue ex vivo, highlighting its potential as a biohybrid electrode coating. This work lays the foundation for the development of biologically guided biohybrid interfaces, towards seamless integration with the nervous system.