Journal
ACS NANO
Volume 16, Issue 2, Pages 1986-1998Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c06892
Keywords
aligned fibrous hydrogels; adhesive capacity; spatiotemporal delivery; neural stem/progenitor cell; spinal cord injury repair
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Funding
- National Natural Science Foundation of China [81891002, 81771338, 32071338]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16040700]
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Aligned collagen-fibrin hydrogels with stretchable property, adhesive behavior, and controlled delivery capability were developed for spinal cord injury repair. The hydrogels demonstrated improved mechanical properties compared to collagen-only hydrogels and promoted endogenous neural stem/progenitor cell migration and differentiation, leading to effective recovery.
Aligned fibrous hydrogels capable of recruiting endogenous neural stem/progenitor cells (NSPCs) show great promise in spinal cord injury (SCI) repair. However, the hydrogels suffer from severe issues in close contact with the transected nerve stumps and harnessing the NSPC fate in the lesion microenvironment. Herein, we report aligned collagen-fibrin (Col-FB) fibrous hydrogels with stretchable property, adhesive behavior, and stromal cell-derived factor-1 alpha (SDF1 alpha)/paclitaxel (PTX) spatiotemporal delivery capability. The resultant Col-FB fibrous hydrogels exhibited 1.98 times longer elongation at break (230%), 2.55 times lower Young's modulus (17.93 +/- 1.16 KPa), and 2.21 times greater adhesive strength (3.45 +/- 0.48 KPa) than collagen (Col) fibrous hydrogels. The soft aligned fibrous hydrogels simulate the oriented microstructure and soft tissue feature of a natural spinal cord and provide elasticity and adhesivity to ensure a persistent close contact with host stumps. The repair of complete transection SCI in rats demonstrates that middle-to-bilateral SDFI alpha gradient release induced endogenous NSPC migration to the lesion site in 10 days, and SDFI alpha/PTX sequential release promoted neuronal differentiation of the recruited NSPCs over 8 weeks, leading to hind limb locomotion recovery. The presented strategy was proved to be efficient for harnessing endogenous NSPCs, which facilitate SCI repair significantly.
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