title: Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration.
abstract: Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G' than G″ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells (NPCs)/stem cells (NSCs) fully embedded in the 3D-IKVAV/-RGD nanofiber hydrogel survived, whereas those embedded within the RADA 16-I hydrogel hardly survived. Moreover, the -IKVAV/-RGD nanofiber hydrogel supported NPC/NSC neuron and astrocyte differentiation in a 3D environment without adding extra growth factors. Studies of three nerve injury models, including sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection, indicated that the designer -IKVAV/-RGD nanofiber hydrogel provided a more permissive environment for nerve regeneration than the RADA 16-I hydrogel. Therefore, we reported a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration.
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, College of Life Science and Technology, Jinan University , Guangzhou, Guangdong, 510632, China.
authors.forename: Yuqiao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Biomedical Science, LKS Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR, 000000, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Biomedical Science, LKS Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR, 000000, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University , Guangzhou, Guangdong, 510632, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, College of Life Science and Technology, Jinan University , Guangzhou, Guangdong, 510632, China.
authors.forename: Yongnu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Songying
authors.initials: S
authors.lastname: Ouyang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Song
authors.affiliation: School of Biomedical Science, LKS Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR, 000000, PR China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Fang
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University , Guangzhou, Guangdong, 510632, China.|Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore , Singapore , 117576.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Seeram
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, College of Life Science and Technology, Jinan University , Guangzhou, Guangdong, 510632, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, College of Life Science and Technology, Jinan University , Guangzhou, Guangdong, 510632, China.|School of Biomedical Science, LKS Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR, 000000, PR China.
authors.forename: Liumin
authors.initials: L
authors.lastname: He
authors.affiliation: School of Biomedical Science, LKS Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR, 000000, PR China.|Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University , Guangzhou, Guangdong, 510632, China.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong , Pokfulam, Hong Kong SAR, 000000, PR China.
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000188:drug therapy*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017433:Protein Structure, Secondary; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D020100:Hydrogels; D010455:Peptides; C546681:RADA16-I; D049452:Green Fluorescent Proteins
keywords: 3D cell culture; hydrogel; nanofiber; nerve regeneration; self-assembling peptides