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Peptide‐mediated surface coatings for the release of wound‐healing cytokines

Supporting the wound healing process by sending the appropriate cytokine signals can shorten healing time and overcome chronic inflammation syndromes. Even though adhesion peptides consisting of Arg‐Gly‐Asp (RGD) are commonly used to enhance cell‐surface interactions, peptide‐mediated cytokine delivery has not been widely exploited so far. Cytokines interact with high affinity with their cognitive receptors but also with sulfated glycosaminoglycans (GAGs), both of which form a base for incorporation of cytokines into functional biomaterials. Here, we report on a mussel‐derived surface coating as a prospective cytokine delivery system using covalently bound heparin mimetics, receptor‐derived chemokine‐binding peptides, and heparin‐binding peptides (HBP). The latter enabled non‐covalent immobilization of heparin on the surface followed by chemokine binding and release, whereas the former allowed direct non‐covalent chemokine immobilization. The peptide displayed excellent binding to custom‐made polystyrene 96‐well plates, enabling convenient testing of several compounds. Released chemokine successfully induced migration in Jurkat cells, especially for the non‐covalent heparin immobilization approach using HBPs as evaluated in a transwell assay. In comparison, heparin‐mimetic coatings, comprised of sulfated peptides and GAG derivatives, proved less efficient with respect to amount of immobilized chemokine and migratory response. Thus, our study provides a roadmap for further rational optimization and translation into clinics.1.


(a) Chemical structure of mussel‐derived peptide (MP(+)). The l‐3,4‐dihydroxyphenylalanine (DOPA) units for surface binding are highlighted in green, and the biotin‐tag for detection in gray. Functional groups for peptide conjugation by thiol‐maleimide Michael addition reaction and Cu(I)‐catalyzed azide‐alkine cycloaddition (CuAAC) are highlighted in red and blue, respectively. (b) Surface binding of the mussel‐derived anchor peptide MP(+) to polystyrene. MP(−), a tyrosine‐containing peptide analog, shows a 20‐fold loss in affinity in comparison to the DOPA‐containing derivative. n = 3, *p ≤ 0.05, ***p ≤ 0.001 with respect to MP(−)
A binding affinity study revealed a 20‐fold shift in EC50 between the peptides
  1. Clauder, F, Möller, S, Köhling, S, et al. Peptide‐mediated surface coatings for the release of wound‐healing cytokines. J Tissue Eng Regen Med. 2020; 14: 1738– 1748. https://doi.org/10.1002/term.3123