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Electrical stimulation (ES) can be used to manipulate recovery after peripheral nerve injuries. Although biomaterial-based strategies have already been implemented to gain momentum for ES and engineer permissive microenvironments for neural regeneration, the development of biomaterials for specific stimuli-responsive modulation of neural cell properties remains a challenge. Herein, we homogeneously incorporate pristine carbon nanotubes into a functional self-assembling peptide to prepare a hybrid hydrogel with good injectability and conductivity. Two-dimensional (on the surface) and three-dimensional (within the hybrid hydrogel) culturing experiments demonstrate that ES promotes axon outgrowth and Schwann cell (SC) migration away from dorsal root ganglia spheres, further revealing that ES-enhanced interactions between SCs and axons result in improved myelination. Thus, our study not only advances the development of tailor-made materials but also provides useful insights into comprehensive approaches for promoting nerve growth and presents a practical strategy of repairing peripheral nerve injuries.

In the current study, we present three designer self-assembling peptides (SAPs) by appending RADA 16-I with epitopes IKVAV, RGD, and YIGSR, which have different net charges and amphiphilic properties at neutral pH. The self-assembly of the designer SAPs is intensively investigated as a function of pH, canion type, and assembly time. The morphologies of the designer SAPs were studied by atomic force microscope. The secondary structure was investigated by circular dichroism. The dynamic viscoelasticity of designer SAP solutions was examined during titration with different alkaline reagents. Our study indicated that both electrostatic and hydrophilic/hydrophobic interactions of the motifs exhibited influences on the self-assembly, consequentially affecting the fiber morphologies and rheological properties. Moreover, NaOH induced a quicker assembly/reassembly of the designer SAPs than Tris because of its strong ionic strength. Therefore, our study gained comprehensive insight into the self-assembling mechanism as references for developing RADA 16-I-based functional SAPs.

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RADA16-I (Ac-(RADA)-CONH) is a widely investigated self-assembling peptide (SAP) in the biomedical field. It can undergo ordered self-assembly to form stable secondary structures, thereby further forming a nanofiber hydrogel. The modification of RADA16-I with functional peptide motifs has become a popular research topic. Researchers aim to exhibit particular biomedical signaling, and subsequently, further expand its applications. However, only a few fundamental reports are available on the influences of the peptide motifs on self-assembly mechanisms of designer functional RADA16-I SAPs. In this study, we designed RGD-modified RADA16-I SAPs with a series of net charges and amphiphilicities. The assembly/reassembly of these functionally designer SAPs was thoroughly studied using Raman spectroscopy, CD spectroscopy, and AFM. The nanofiber morphology and the secondary structure largely depended on the balance between the hydrophobic effects versus like-charge repulsions of the motifs, which should be to the focus in order to achieve a tailored nanostructure. Our study would contribute insight into considerations for sophisticated design of SAPs for biomedical applications.

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