Hierarchically aligned fibrin nanofiber hydrogel accelerated axonal regrowth and locomotor function recovery in rat spinal cord injury

Abstract

BackgroundDesigning novel biomaterials that incorporate or mimic the functions of extracellular matrix to deliver precise regulatory signals for tissue regeneration is the focus of current intensive research efforts in tissue engineering and regenerative medicine.Methods and resultsTo mimic the natural environment of the spinal cord tissue, a three-dimensional hierarchically aligned fibrin hydrogel (AFG) with oriented topography and soft stiffness has been fabricated by electrospinning and a concurrent molecular self-assembling process. In this study, the AFG was implanted into a rat dorsal hemisected spinal cord injury model to bridge the lesion site. Host cells invaded promptly along the aligned fibrin hydrogels to form aligned tissue cables in the first week, and then were followed by axonal regrowth. At 4 weeks after the surgery, neurofilament (NF)-positive staining fibers were detected near the rostral end as well as the middle site of defect, which aligned along the tissue cables. Abundant NF- and GAP-43-positive staining indicated new axon regrowth in the oriented tissue cables, which penetrated throughout the lesion site in 8 weeks. Additionally, the abundant blood vessels marked with RECA-1 had reconstructed within the lesion site at 4 weeks after surgery. Basso-Beattie-Bresnahan scoring showed that the locomotor performance of the AFG group recovered much faster than that of blank control group or the random fibrin hydrogel (RFG) group from 2 weeks after surgery. Furthermore, diffusion tensor imaging tractography of MRI confirmed the optimal axon fiber reconstruction compared with the RFG and control groups.ConclusionTaken together, our results suggested that the AFG scaffold provided an inductive matrix for accelerating directional host cell invasion, vascular system reconstruction, and axonal regrowth, which could promote and support extensive aligned axonal regrowth and locomotor function recovery.

<p>An anti-inflammatory peptide and brain-derived neurotrophic factor-modified hyaluronan-methylcellulose hydrogel promotes nerve regeneration in rats with spinal cord injury</p>

“…As they lack an extracellular matrix and vascularization, cystic cavities do not promote regeneration of axons Hydrogels are biocompatible implants that have been used for creating a permissive environment, and bridging lesion cavities, by releasing neurotrophic substances. Yao et al 43 implanted an AFG hydrogel into a rat hemisected SCI model to bridge lesion cavities, which promoted axonal regeneration and locomotor function recovery of rats. Xu et al 44 demonstrated that FGF2loaded dscECM-HP hydrogel can achieve sustained release of FGF2 in vitro and recover both nerve tissue morphology and neuron functions in vivo.…”

Beyond 2D: effects of photobiomodulation in 3D tissue-like systems

“…[66][67][68] Various 3D structures can be formed from the fibrin gel, in particular, by molding and electrospinning methods. 69,70 Moreover, the degradation rate of this hydrogel can be controlled locally, by, for example, the addition of fibrinolysis inhibitors. 71,72 Various modifications of the hydrogel can help in directing the differentiation of cells, in particular, in the angiogenic direction.…”

Hydrogel and neural progenitor cell delivery supports organotypic fetal spinal cord development in an ex vivo model of prenatal spina bifida repair

“…5,61,77,78 In addition, the ideal hydrogel product should be injectable and capable of filling any cavity defects specific to the fetus, thereby providing a scaffolding to bridge damaged axons within the spinal cord. 79 One drawback of fibrin hydrogels has been the rapid degradation by native plasmin over the first several weeks after application. 80,81 Although modifying the chemical properties of our hydrogels may extend its degradation until there is complete ingrowth of adjacent epithelium, another strategy to circumvent short degradation times would be to employ a biodegradable sheet on top of the hydrogel patch.…”