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Systematic d-Amino Acid Substitutions to Control Peptide and Hydrogel Degradation in Cellular Microenvironments.

Kartik BombQi ZhangEden M FordCatherine A FromenApril M Kloxin
Published in: ACS macro letters (2023)
Enzymatically degradable peptides are commonly used as linkers within hydrogels for biological applications; however, controlling the degradation of these engineered peptides with different contexts and cell types can prove challenging. In this work, we systematically examined the substitution of d-amino acids (D-AAs) for different l-amino acids in a peptide sequence commonly utilized in enzymatically degradable hydrogels (VPMS↓MRGG) to create peptide linkers with a range of different degradation times, in solution and in hydrogels, and investigated the cytocompatibility of these materials. We found that increasing the number of D-AA substitutions increased the resistance to enzymatic degradation both for free peptide and peptide-linked hydrogels; yet, this trend also was accompanied by increased cytotoxicity in cell culture. This work demonstrates the utility of D-AA-modified peptide sequences to create tunable biomaterials platforms tempered by considerations of cytotoxicity, where careful selection and optimization of different peptide designs is needed for specific biological applications.
Keyphrases
  • amino acid
  • drug delivery
  • tissue engineering
  • stem cells
  • single cell
  • hydrogen peroxide
  • atomic force microscopy