A Thermosensitive Heparin-Poloxamer Hydrogel Bridges aFGF to Treat Spinal Cord Injury

Abstract

Acidic fibroblast growth factor (aFGF) exerts a protective effect on spinal cord injury (SCI) but is limited by the lack of physicochemical stability and the ability to cross the blood spinal cord barrier (BSCB). As promising biomaterials, hydrogels contain substantial amounts of water and a three-dimensional porous structure and are commonly used to load and deliver growth factors. Heparin can not only enhance growth factor loading onto hydrogels but also can stabilize the structure and control the release behavior. Herein, a novel aFGF-loaded thermosensitive heparin-poloxamer (aFGF-HP) hydrogel was developed and applied to provide protection and regeneration after SCI. To assess the effects of the aFGF-HP hydrogel, BSCB restoration, neuron and axonal rehabilitation, glial scar inhibition, inflammatory response suppression, and motor recovery were studied both in vivo and in vitro. The aFGF-HP hydrogels exhibited sustained release of aFGF and protected the bioactivity of aFGF in vitro. Compared to groups intravenously administered either drug-free HP hydrogel or aFGF alone, the aFGF-HP hydrogel group revealed prominent and attenuated disruption of the BSCB, reduced neuronal apoptosis, reactive astrogliosis, and increased neuron and axonal rehabilitation both in vivo and in vitro. This work provides an effective approach to enhance recovery after SCI and provide a successful strategy for SCI protection.