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

FGFP/TIMP-AMP self-assembled into a hydrogel under physiological conditions with suitable pore size for cell growth.

• The hydrogel comprised three components: a basic fibroblast growth factor-mimetic peptide (FGFP), an angiopoietin-1-mimetic peptide (AMP), and a microenvironment-responsive TIMP sequence targeting MMP-2.
• Assembly occurred under physiological conditions, producing a pore structure compatible with cell growth.
• The TIMP sequence was designed to be responsive to MMP-2, which is upregulated in ischemic microenvironments.

FGFP/TIMP-AMP hydrogel significantly promoted HUVEC migration and tube formation in vitro.

• Human umbilical vein endothelial cells (HUVECs) were used as the in vitro angiogenesis model.
• Both migration assays and tube formation assays demonstrated significant promotion compared to controls.
• These effects reflect the angiogenic properties attributed to the AMP and FGFP components of the hydrogel.

FGFP/TIMP-AMP hydrogel reduced apoptosis and protected PC12 cells against hypoxia in an oxygen-glucose deprivation (OGD) model.

• PC12 cells subjected to oxygen and glucose deprivation (OGD) were used as an in vitro ischemia model.
• Treatment with FGFP/TIMP-AMP effectively reduced apoptosis in OGD-exposed PC12 cells.
• The hydrogel provided neuroprotective effects against hypoxic conditions in this cell model.

FGFP/TIMP-AMP hydrogel enhanced neuronal survival in a middle cerebral artery occlusion (MCAO) rat model of ischemic stroke.

• The MCAO rat model was used as the in vivo ischemic stroke model.
• Morphological assessments demonstrated enhanced neuronal survival following hydrogel treatment.
• The neuroprotective effect in vivo was consistent with the anti-apoptotic findings observed in vitro.

FGFP/TIMP-AMP hydrogel promoted vascular regeneration in the MCAO rat model.

• Vascular regeneration was assessed morphologically in MCAO rat brain tissue.
• The hydrogel treatment resulted in enhanced vascular regeneration compared to controls.
• This effect is attributed to the combined angiogenic actions of the FGFP and AMP components.

FGFP/TIMP-AMP hydrogel promoted blood-brain barrier (BBB) repair in MCAO rats.

• BBB integrity was assessed morphologically in the MCAO rat model.
• Hydrogel treatment resulted in improved BBB repair compared to control conditions.
• BBB repair is a critical component of recovery following ischemic stroke, and the TIMP-AMP components may contribute through MMP-2 modulation.

Morphological improvements from FGFP/TIMP-AMP hydrogel treatment corresponded with recovery of motor function in behavioral tests in MCAO rats.

• Behavioral tests were conducted to assess motor function recovery in MCAO rats.
• Animals treated with FGFP/TIMP-AMP hydrogel showed improved motor function compared to controls.
• The functional improvements paralleled the morphological findings of enhanced neuronal survival, vascular regeneration, and BBB repair.