Self-Assembling Hydrogel for Controlled Release of bFGF and Ang-1 Mimetic Peptide Promotes Neurovascular Repair in Ischemic Stroke Rats

Self-assembling peptide hydrogels represent a promising strategy for growth factor delivery and tissue repair, with the advantage of sustained release and micro-environment response characteristics. In the present study, a multiple biofunctional self-assembling hydrogels-FGFP/TIMP-AMP was constructed, which comprised three key components: (1) a basic fibroblast growth factor-mimetic peptide (FGFP), (2) an angiopoietin-1-mimetic peptide (AMP), and (3) a microenvironment-responsive TIMP sequence designed to target MMP-2. The FGFP/TIMP-AMP could assemble into a hydrogel under physiological conditions with a suitable pore size for cell growth. In vitro, it significantly promoted HUVEC migration and tube formation. Using a PC12 deprivation of oxygen and glucose (OGD) model, it effectively reduced apoptosis and protected against hypoxia. Furthermore, the bFGF/TIMP-AMP assembling hydrogels enhanced neuronal survival, vascular regeneration, and blood–brain barrier (BBB) repair in a middle cerebral artery occlusion (MCAO) rat model. These morphological improvements further promoted the recovery of motor function in behavioral tests. Therefore, these results highlighted the therapeutic potential of FGFP/TIMP-AMP assembling hydrogel for the repair of ischemic stroke.