Abstract
The reconstruction of peripheral nerves has lately received great attention as many patients suffer from peripheral nerve injury every year around the world. However, the damage to human nerve cells has different degrees of irreversibility due to a slow growth speed and low adhesion with the surrounding tissues. In an effort to overcome this challenge, we applied novel laminin (LN)-modified thiolated gellan gum (TGG) and loaded the nerve growth factor (NGF) as a tissue engineering scaffold for facilitating neuronal stem cell proliferation via a synergy effect for the ERK–MAPK pathway. TGG was characterized by 1H NMR spectroscopy and scanning electron microscopy, and its rheological behavior was also studied. The NGF release curve fitted the Korsmeyer–Peppas model and belonged to a Fickian diffusion-controlled release mechanism. The neuronal stem cells from newborn SD rats could adhere tightly and proliferate at a relatively rapid speed, showing excellent biocompatibility and the ability to promote growth in the modified TGG. LN and NGF could decrease the apoptosis effects of neuronal stem cells, as shown via the flow cytometry results. In a three-dimensional culture environment, LN and NGF could facilitate neuronal stem cells to differentiate into neurons, as proved by immunofluorescence, q-PCR, and western blot analyses. Therefore, the rational design of the TGG gel loaded with NGF has promising applications in the reconstruction of peripheral nerves.
Highlights
Peripheral nerve injury is a common type of injury in surgery
We investigated the proliferation behavior and apoptosis process induced by LNmodi ed gellan gum hydrogels and explored the synergy mechanism for the ERK–MAPK pathway
thiolated gellan gum (TGG) was characterized by 1H NMR spectroscopy to exactly determine its chemical structure, with the measurement performed on a Bruker 500 MHz Ascend system
Summary
Growth factor (NGF), gene therapy,[4] nanotherapy,[5] etc This still cannot change the fact that human peripheral nerve regeneration is difficult and the growth is slow, and the repair of peripheral nerve injury still needs our continuous efforts for further development and improvement.[6] Among the numerous treatments, the use of tissue engineering scaffolds has been spotlighted for supporting the controlled release of neurotrophic factors and enhancing the growth of neurons or neuronal stem cells. We used modi ed gellan gum (TGG) loaded with laminin (LN) and nerve growth factor (NGF) to enhance the proliferation and differentiation of neuronal stem cells via a synergistic reinforcement mechanism. The prepared TGG gel has promising applications in NGF delivery and can provide new opportunities for peripheral nerve injury treatment in clinical applications
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