This work combines the wound-healing-related properties
of the
host defense peptide KR-12 with wood-derived cellulose nanofibrils
(CNFs) to obtain bioactive materials, foreseen as a promising solution
to treat chronic wounds. Amine coupling through carbodiimide chemistry,
thiol-ene click chemistry, and Cu(I)-catalyzed azide-alkyne cycloaddition
were investigated as methods to covalently immobilize KR-12 derivatives
onto CNFs. The effects of different coupling chemistries on the bioactivity
of the KR12-CNF conjugates were evaluated by assessing their antibacterial
activities againstEscherichia coliandStaphylococcus aureus. Potential
cytotoxic effects and the capacity of the materials to modulate the
inflammatory response of lipopolysaccharide (LPS)-stimulated RAW 245.6
macrophages were also investigated. The results show that KR-12 endowed
CNFs with antibacterial activity againstE. coliand exhibited anti-inflammatory properties and those conjugated
by thiol-ene chemistry were the most bioactive. This finding is attributed
to a favorable peptide conformation and accessibility (as shown by
molecular dynamics simulations), driven by the selective chemistry
and length of the linker in the conjugate. The results represent an
advancement in the development of CNF-based materials for chronic
wound care. This study provides new insights into the effect of the
conjugation chemistry on the bioactivity of immobilized host defense
peptides, which we believe to be of great value for the use of host
defense peptides as therapeutic agents.