An ECM‐Mimicking, Injectable, Viscoelastic Hydrogel for Treatment of Brain Lesions

Abstract Brain lesions can arise from traumatic brain injury, infection, and craniotomy. Although injectable hydrogels show promise for promoting healing of lesions and health of surrounding tissue, enabling cellular ingrowth and restoring neural tissue continue to be challenging. It is hypothesized that these challenges arise in part from the mismatch of composition, stiffness, and viscoelasticity between the hydrogel and the brain parenchyma, and this hypothesis is tested by developing and evaluating a self‐healing hydrogel that not only mimics the composition, but also the stiffness and viscoelasticity of native brain parenchyma. The hydrogel is crosslinked by dynamic boronate ester bonds between phenylboronic acid grafted hyaluronic acid (HA‐PBA) and dopamine grafted gelatin (Gel‐Dopa). This HA‐PBA/Gel‐Dopa hydrogel could be injected into a lesion cavity in a shear‐thinning manner with rapid hemostasis, high tissue adhesion, and efficient self‐healing. In an in vivo mouse model of brain lesions, the multi‐functional injectable hydrogel is found to support neural cell infiltration, decrease astrogliosis and glial scars, and close the lesions. The results suggest a role for extracellular matrix‐mimicking viscoelasticity in brain lesion healing, and motivate additional experimentation in larger animals as the technology progresses toward potential application in humans.