Modulation of Human CXCL12 Binding Properties to GlycosaminoglycansTo Enhance Chemotactic Gradients

Controlled release of active biomolecules is an attractive approach to modulate chemotactic gradients and accordingly the recruitment of cells, e.g. endothelial progenitor cells to improve wound healing or stimulate angiogenesis after myocardial infarction. Here, we developed variants of hCXCL12, also named stromal cell-derived factor 1α, a chemokine that activates the CXCR4 and consequently recruits tissue specific stem and progenitor cells. hCXCL12 variants were designed to bind to glycosaminoglycans (GAGs) with different affinities in order to modulate its release. Sixteen analogs were recombinantly produced, characterized, and tested for their GAG-binding property. The most promising variants hCXCL12 K24/K27/R41/R47A and hCXCL12 Q48K were used for release studies from starPEG-heparin-hydrogels. The reduced GAG affinity led to a fast release of hCXCL12 K24/K27/R41/R47A, whereas hCXCL12 Q48K was slowly released over 2 weeks due to its increased binding strength compared to wild type hCXCL12. Migration o...