Abstract
The delivery of chemotactic signaling molecules via customized biomaterials can effectively guide the migration of cells to improve the regeneration of damaged or diseased tissues. Here, we present a novel biohybrid hydrogel system containing two different sulfated glycosaminoglycans (sGAG)/sGAG derivatives, namely either a mixture of short heparin polymers (Hep-Mal) or structurally defined nona-sulfated tetrahyaluronans (9s-HA4-SH), to precisely control the release of charged signaling molecules. The polymer networks are described in terms of their negative charge, i.e. the anionic sulfate groups on the saccharides, using two parameters, the integral density of negative charge and the local charge distribution (clustering) within the network. The modulation of both parameters was shown to govern the release characteristics of the chemotactic signaling molecule SDF-1 and allows for seamless transitions between burst and sustained release conditions as well as the precise control over the total amount of delivered protein. The obtained hydrogels with well-adjusted release profiles effectively promote MSC migration in vitro and emerge as promising candidates for new treatment modalities in the context of bone repair and wound healing.
Highlights
We aimed at developing sulfated glycosaminoglycans (sGAG)-based matrices with adjustable charge density and distribution to tune the release of stromal cell-derived factor 1 (SDF-1) and stimulate and control mesenchymal stem cells (MSC) migration
Synthesis and characterization of the hydrogels with precisely controlled charge properties The biohybrid hydrogels were formed through a Michael type addition click reaction between end-functionalized 4arm starPEG-thiol (PEG-SH) and end-functionalized 8arm starPEG-maleimide (PEG-Mal)
We have developed a sGAG-based hydrogel system that allows for a flexible adjustment of the density and distribution of negative charge within the polymer network
Summary
Sulfated glycosaminoglycans (sGAG) are essential components of the extracellular matrix (ECM) and are the key to many signaling processes in tissue development, homeostasis, disease and regeneration (Häcker et al 2005; Meneghetti et al 2015; Raman et al 2005; Richter et al 2018). sGAG-protein interactions are well known to be dominated by electrostatic interactions between the negatively charged GAG, containing anionic sulfate groups, and positively charged domains on the protein surface, structural parameters such as the spatial distribution and position of ionized groups and hydrophobic interactions contribute as well (Björk and Lindahl 1982; Capila and Linhardt 2002; Garg et al 2005; Köhling et al 2016b; Künze et al 2016; Panitz et al 2016; Proudfoot et al 2017; Walkowiak et al 2020). Sulfated glycosaminoglycans (sGAG) are essential components of the extracellular matrix (ECM) and are the key to many signaling processes in tissue development, homeostasis, disease and regeneration (Häcker et al 2005; Meneghetti et al 2015; Raman et al 2005; Richter et al 2018). Charge carriers are not distributed homogenously but rather reside as local clusters with specific patterns represented by rather long sulfated polysaccharides, i.e. sGAG such as heparan sulfate or the closely related heparin (Richter et al 2018).
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