Transforming Growth Facto beta-1 Binding by Peptide Amphiphile Hydrogels

Jacob A. Lewis, Ronit Freeman, James K. Carrow, Tristan D. Clemons, Liam C. Palmer, Samuel Stupp

Research output: Contribution to journalArticle

Abstract

Supramolecular biomaterials are promising systems to bind or deliver therapeutic growth factors given their great structural versatility and tunability of properties by simply mixing molecules. In this work, we have investigated this approach for the growth factor cytokine TGF beta-1, which is potentially important in the regeneration of damaged cartilage or in the prevention of fibrinogenesis of organs and the progression of tumors. Our previous work identified a peptide sequence capable of binding TGF beta-1 and supramolecular peptide amphiphile (PA) nanofiber hydrogels that displayed the sequence were found to enhance regeneration of cartilage in a rabbit model. In this work, we have synthesized novel PA molecules motivated by the tendency of the original bioactive peptide to undergo deamidation during purification procedures, thus interfering with synthesis of molecularly well-defined structures. We report here on novel PA nanofibers that can be purified without deamidation to establish if the chemical reaction affects chondrogenesis. Interestingly, we found that gels formed from nanofibers displaying a fully deamidated sequence by introducing an asparagine to aspartic acid mutation retain 25% more growth factor relative to those displaying the original bioactive peptide even though the individual peptides have similar affinity for the cytokine. We attribute this difference in growth factor retention to bundling of nanofibers displaying the original asparagine-containing sequence, thus masking the growth factor-binding structure. Improved retention of the growth factor resulted in chondrogenesis of cells encapsulated in the gels as indicated by a more than 50% increase in Sox 9 expressing cells at 3 days and a 100% increase in glycosaminoglycan production at 21 days. We have therefore been able to design a more effective bioactive supramolecular biomaterial to bind TGF beta-1, and also demonstrated how bioactive peptide sequences in supramolecular biomaterials can have impact on their structure at larger length scales that change their biological functions.

Original languageEnglish
Pages (from-to)4551-4560
Number of pages10
JournalACS Biomaterials Science and Engineering
Volume6
Issue number8
DOIs
Publication statusPublished - Aug 2020
Externally publishedYes

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