Producing gradients of biological cues into nerve conduits is crucial for nerve guidance and regeneration. Herein, the fabrication of gradients of stromal cell-derived factor-1α (SDF1α) on electrospun collagen mats is reported using an electrohydrodynamic jet printing technique. The fabrication of various SDF1α gradated patterns on collagen fibrous mats is successfully demonstrated including shallow continuous gradient, steep continuous gradient, and step gradient by controlling the processing parameters. The SDF1α graded collagen scaffolds show a long-term stable gradient, as SDF1α is fused with a unique peptide of collagen binding domain (CBD), and CBD-SDF1α can specifically bind to the collagen mat. Such graded scaffolds exhibit sustained release of SDF1α. Further examination of neural stem cell (NSC) response to the CBD-SDF1α gradients with various patterns show that the NSCs can sense the CBD-SDF1α gradients, display a polarized morphology, and tend to migrate toward the region with a higher CBD-SDF1α content. The collagen mats with CBD-SDF1α gradients guide gradual distribution of NSCs, and NSC-differentiated neurons and astrocytes after seeding for 1 and 7 d. This new class of CBD-SDF1α gradient scaffolds can potentially be employed for guided nerve regeneration.
Keywords: collagen-binding domain; directed migration; neural stem cells; protein gradients.
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