Slow and sustained release of active cytokines from self-assembling peptide scaffolds

Fabrizio Gelain, Larry D. Unsworth, Shuguang Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Controlling the cellular microenvironment is thought to be critical for the successful application of biomaterials for regenerative medicine strategies. Self-assembling peptides are proving to be a promising platform for a variety of regenerative medicine applications. Specifically, RADA16-I self-assembling peptides have been successfully used for 3D cell culture, accelerated wound healing, and nerve-repair. Understanding the fundamental mechanisms for protein mobility within, and ultimately release from, this nanostructured system is a critical aspect for controlling cellular activity; studies which are largely lacking within the literature. Herein, we report that designer self-assembling peptide scaffolds facilitate slow and sustained release of active cytokines that are extremely relevant to many areas of regenerative medicine. In addition, multiple diffusive mechanisms are observed to exist for human βFGF, VEGF and BDNF within RADA16-I and two different RADA16-I nanofiber forming peptides with net positive or negative charges located at the C-terminus. In some cases, two populations of diffusing molecules are observed at the molecular level: one diffusing fully within the solvent, and another that exhibits hindered mobility. Results suggest that protein mobility is inhibited by both physical hinderances and charge induced interactions between the protein and peptide nanofibers. Moreover, assays using adult neural stem cells (NSCs) are employed to assess the functional release of active cytokine (βFGF) up to three weeks. Our results not only provide evidence for long-term molecular release from self-assembling peptide scaffolds but also inspiration for a plethora of slow molecular release strategies for clinical applications.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
JournalJournal of Controlled Release
Volume145
Issue number3
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Cytokines
  • Drug release
  • Neural stem cells
  • Self-assembling peptides

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine(all)

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