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

Abstract

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.

Amphiphilic Copolymers for Versatile, Facile, and In Situ Tunable Surface Biofunctionalization

“…[ 22 ] Dihydroxyphenylalanine (DOPA)‐containing anchor peptides were utilized to tether heparin‐binding peptides, sulfated hyaluronic acid derivatives, sulfated peptides, and receptor‐derived chemokine binding peptides for stromal‐cell‐derived factor 1 binding to polystyrene tissue culture plates. [ 23 ] A self‐strengthening hydrophobic anchoring unit based on thermal merocyanine‐to‐spiropyran isomerization was combined with adhesion ligand (RGD) peptides to functionalize surfaces, allowing for the fine‐tuned mechanical stimulation of adhering mesenchymal stromal cells. [ 24 ]…”

Chemical Modification of Hyaluronan and Their Biomedical Applications

“…The most frequently used techniques for this type of GAG functionalization are currently hydrazone (Altgärde et al, 2013;Peerboom et al, 2017) and oxime (Novoa-Carballal and Müller, 2012;Thakar et al, 2014) ligation chemistry. Another procedure uses reductive amination with e.g., ethylendiamine dihydrochloride and sodium cyanoborohydride (Clauder et al, 2020). Examples of conjugation reactions are presented in Figure 12.…”

Protease-Triggered Release of Stabilized CXCL12 from Coated Scaffolds in an Ex Vivo Wound Model

“…Heparin-based PEG hydrogels loaded with CXCL12 are often applied [76][77][78], and hydrogels packed with CXCL12 mutants have been proven to attract early endothelial progenitor cells with a long-term release profile upon mutations of the heparin binding site of CXCL12 [26,79]. Other non-covalent approaches used a heparin-based sandwich-like setup, where the chemokine is bound by soluble heparin, which in turn is immobilized by a heparin-binding peptide [30,80]. Here, release kinetics might be more complex due to diffusion of CXCL12 alone or in combination with heparin.…”