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Metal‐chelating affinity hydrogels for sustained protein release
Author(s) -
Lin ChienChi,
Metters Andrew T.
Publication year - 2007
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31282
Subject(s) - self healing hydrogels , materials science , chelation , ligand (biochemistry) , ethylene glycol , dissociation constant , metal ions in aqueous solution , kinetics , metal , biophysics , dissociation (chemistry) , histidine , reaction rate constant , polymer chemistry , chemical engineering , organic chemistry , chemistry , biochemistry , enzyme , receptor , physics , quantum mechanics , metallurgy , biology , engineering
Affinity hydrogels based on poly(ethylene glycol) diacrylate and a metal‐ion‐chelating ligand, glycidyl methacrylate–iminodiacetic acid, have been developed to systematically decrease protein release rates from hydrophilic tissue engineering scaffolds formed in situ . In the current work, tunable and sustained release of a model protein, hexa‐histidine tagged green fluorescence protein (hisGFP), is accomplished by judiciously increasing ligand:protein ratio or replacing low‐affinity nickel ions with high‐affinity copper ions. Agreement between theoretical predictions of a reaction‐diffusion model and experimental measurements confirm metal‐ ion‐mediated sustained protein release from these affinity hydrogels is governed by equilibrium protein–ligand binding affinity (dissociation constant, K d ) as well as protein–ligand dissociation kinetics (protein debinding rate constant, k off ). The former dictates the release rate in the early period of protein release while the latter determines the long‐term sustained release effect. While metal‐ion affinity binding has been widely used for various purposes including protein purification and surface patterning, this is the first report describing its application in systematically controlling protein release from hydrophilic PEG networks suitable for cell encapsulation. By using ligands with proper binding kinetic constants ( K d and k off ), localized protein delivery can be sustained over clinically relevant timescales while maintaining a favorable environment for cell encapsulation and viability. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007