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Molecular Transport and Binding in Hydrogels

Biohybrid hydrogels consisting of electrically neutral synthetic polymers, e. g. star-shaped poly(ethylene glycol) (starPEG), and highly anionic glycosaminoglycans (GAGs) offer exciting options for regenerative therapies as they allow for the electrostatic conjugation of various growth factors. We establish analytical methods and numerical models that provide insights into correlations between the protein transport and the molecular composition and structure of hydrogels. These models are further used to predict the spatially and timely distribution of morphogens under application conditions.

 

Tunable release of the platelet-derived growth factor (PDGF-BB) from the starPEG-GAG hydrogels: (A) Schematic representation of the selective removal of heparin’s sulfate groups at one or more positions, resulting in different degrees of sulfation (DS). (B) Plot of dissociation rate constants, kd, vs the association rate constants, ka, for Kd values (KD = kd/ka) obtained from biolayer interferometry (BLI) for the interaction of PDGF-BB with the heparin derivatives. In combination with the dashed lines, the circles indicate the rate constants kd and ka determined via BLI. The solid lines represent all possible combinations of ka and kd associated with the given Kd values. The parameter τ is the residence time, characterizing the life time of the PDGF-BB-heparin complexes. (C) Release of PDGF-BB from hydrogels formed from starPEG and heparin derivatives. Circles represent experimental data and the solid lines release profiles calculated on the basis of a reaction-diffusion model. The release experiments were performed in low protein binding tubes, see inset. The volume shown in red represents the hydrogels and the volume shown in blue the release medium. Adapted from [1] with permission, Copyright Elsevier, 2018.

 

References:

[1] Atalah et al. Biomaterials 2018, 181, 227, doi: https://doi.org/10.1016/j.biomaterials.2018.07.056

[2] Zimmermann et al. Polymers 2018, 10, 1376, doi: https://doi.org/10.3390/polym10121376