bFGF-Sodium Hyaluronate Collagen Scaffolds Enable the Formation of Nascent Neural Networks After Adult Spinal Cord Injury

: Neural circuit reconstruction is the main target of functional restoration after adult spinal cord injury (SCI). The microenvironment after adult SCI is hostile to neural regeneration. Here, we designed a bFGF controlled releasing system (bFGF-CRS) by loading bFGF onto the sodium hyaluronate collagen scaffolds to modify the hostile microenvironment. We found that the bFGF-CRS scaffolds had proper mechanical properties for spinal cord regeneration and could slowly release bFGF for up to 6 weeks under the physiological condition. After implantation, the bFGF-CRS scaffolds could reduce microglial activation, promote revascularization, elicit endogenous neurogenesis and promote regrowth of transected axons. The endogenous mature newly born neurons could form synaptic-like connections with each other or with host neurons, including cortex neurons, brainstem neurons and spinal interneurons. The functional nascent neural networks between the lesion area and the host spinal cord were established. It eventually led to hindlimb locomotion recovery. Our study suggests that the bFGF-CRS scaffolds, modifying the microenvironment of the lesion area, can rebuild the damaged neural circuit, thus support great potential for SCI treatment in the clinical application.