Ultrasoft bioadhesive hydrogel as a versatile platform for the delivery of basic fibroblast growth factor to repair traumatic brain injury

Traumatic brain injury (TBI) can disrupt the blood–brain barrier and cause loss of neuronal functions. The neuroprotective effects of exogenous basic fibroblast growth factor (FGF2) have been demonstrated. However, these effects diminish with decreasing FGF2 activity. To address this issue, in this study, a multifunctional system with high affinity for growth factors (GelMA-HDC) was developed to deliver growth factors to the brain and provide protection and regeneration in cases of TBI. The results revealed that GelMA-HDC, an injectable hydrogel consisting of gelatin-methacryloyl (GelMA) and heparin-dopamine conjugate (HDC), had a smaller pore size, higher adhesiveness, and softer mechanical properties than the GelMA hydrogel. Moreover, GelMA-HDC increased the stability of FGF2 and enabled controlled FGF2 release in brain lesions. The FGF2-HDC complex exhibited a robust neuroprotective effect by augmenting the FGF2-FGFR1 signaling pathway. Furthermore, the implantation of GelMA-HDC hydrogels at the lesion site in TBI mice exhibited significant reparative potential, encompassing the regeneration of impaired cortical tissues, suppression of neuroinflammation, promotion of neuronal survival, and rescue of learning and memory functions in mice. Therefore, this study presents initial findings on the use of mussel-inspired GelMA-based hydrogels with high affinity for FGFs to treat TBI. This innovative approach holds significant potential for the clinical use of heparin-binding FGFs for repairing TBI or other neurological diseases.