Design and Evaluation of Short Self-Assembling Depsipeptides as Bioactive and Biodegradable Hydrogels

ACS Omega
Kevin M EckesLaura J Suggs

Abstract

Described herein is the design of a cell-adherent and degradable hydrogel. Our goal was to create a self-assembling, backbone ester-containing analogue of the cell adhesion motif, arginine-glycine-aspartic acid (RGD). Two depsipeptides containing Fmoc (N-(fluorenyl)-9-methoxycarbonyl), Fmoc-FR-Glc-D, and Fmoc-F-Glc-RGD (where "Glc" is glycolic acid) were designed based on the results of integrin-binding affinity and cell interaction analyses. Two candidate molecules were synthesized, and their gelation characteristics, degradation profiles, and ability to promote cell attachment were analyzed. We found that ester substitution within the RGD sequence significantly decreases the integrin-binding affinity and subsequent cell attachment, but when the ester moiety flanks the bioactive sequence, the molecule can maintain its integrin-binding function while permitting nonenzymatic hydrolytic degradation. A self-assembled Fmoc-F-Glc-RGD hydrogel showed steady, linear degradation over 60 days, and when mixed with Fmoc-diphenylalanine (Fmoc-FF) for improved mechanical stiffness, the depsipeptide gel exhibited improved cell attachment and viability. Though the currently designed depsipeptide has several inherent limitations, our results i...Continue Reading

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Citations

Mar 30, 2021·ACS Biomaterials Science & Engineering·Sofia PeressottiRylie A Green
Aug 29, 2019·ACS Omega·Antonio C C RibeiroTatiana D Martins

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Methods Mentioned

BETA
fluorescence microscopy
fluorescence spectroscopy
rheometry
fluorescence imaging

Software Mentioned

GraphPad Prism
ImageJ

Related Concepts

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