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Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration.

Yuqiao Sun1, Wen Li2, Xiaoli Wu2

  • 1Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, College of Life Science and Technology, Jinan University , Guangzhou, Guangdong, 510632, China.

ACS Applied Materials & Interfaces
|January 1, 2016
PubMed
Summary

This study developed neutral pH self-assembling peptide (SAP) nanofiber hydrogels using designer SAPs. These hydrogels support neural progenitor cell survival, differentiation, and nerve regeneration, overcoming limitations of previous low-pH SAPs.

Keywords:
3D cell culturehydrogelnanofibernerve regenerationself-assembling peptides

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Nanotechnology

Background:

  • Self-assembling peptide (SAP) RADA16-I hydrogels have limitations due to low pH, causing cellular damage.
  • Developing neutral pH SAPs is crucial for biocompatibility and effective tissue regeneration.

Purpose of the Study:

  • To create neutral pH nanofiber hydrogels using designer SAPs appended with cell adhesion (RGD) and neurite outgrowth (IKVAV) motifs.
  • To evaluate the biocompatibility, cell differentiation support, and nerve regeneration capabilities of the novel hydrogels.

Main Methods:

  • Synthesized two designer SAPs with opposite net charges at neutral pH.
  • Fabricated nanofiber hydrogels (-IKVAV/-RGD) and characterized their viscoelastic properties.
  • Investigated secondary structures using circular dichroism, FTIR, and Raman spectroscopy.
  • Assessed neural progenitor cell (NPC)/stem cell (NSC) survival and differentiation in 3D hydrogels.
  • Evaluated nerve regeneration in sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection models.

Main Results:

  • The -IKVAV/-RGD nanofiber hydrogel exhibited significantly higher storage modulus (G') than loss modulus (G″), indicating a stable hydrogel structure.
  • Designer SAPs showed specific secondary structures influenced by hydrophobic/hydrophilic properties and electrostatic interactions.
  • NPCs/NSCs exhibited high survival rates in the 3D -IKVAV/-RGD hydrogel, unlike in RADA16-I hydrogels.
  • The -IKVAV/-RGD hydrogel promoted NPC/NSC differentiation into neurons and astrocytes without additional growth factors.
  • The designer hydrogel facilitated nerve regeneration in multiple injury models, outperforming RADA16-I hydrogels.

Conclusions:

  • Developed a novel strategy for synthesizing neutral pH SAP nanofiber hydrogels with enhanced biocompatibility.
  • The -IKVAV/-RGD hydrogel provides a superior microenvironment for 3D cell culture and neural regeneration.
  • This approach offers a promising mechanism for designing advanced SAPs for tissue engineering and regenerative medicine applications.