Development of pH-responsive Hydrogels as Biomaterials

‘Smart’ polymers that controllably respond to external stimuli are particularly attractive as biomaterials. Objective: A degradable polymeric material was required that could be stored for prolonged periods in aqueous environments prior to an ‘on command’ onset of degradation. Potential applications include wound closure, drug delivery and tissue engineering activities. Methods: Model non-degradable crosslinked polymers were prepared by solution copolymerization of acrylic acid, polyethylene glycol methyl ether methacrylate and tetraethylene glycol dimethacrylate. Fully degradable analog polymers were also prepared by the substitution of a degradable crosslinker for the tetraethylene glycol dimethacrylate component in the polymerization process. Degradable crosslinker was obtained by reaction of polyethylene glycol with lactide followed by methacrylate addition. Thermally prepared polymers were washed, dried, weighed and then stored in either distilled water or aqueous buffer at pH of 3, 5 or 7. The samples were periodically removed and weighed to measure water uptake or degradation. Results: In the non-degradable model systems, storage of the polymers in distilled water or pH 3 buffer for several weeks resulted in virtually no swelling. Modest swelling (Q = 5-20) was observed with storage at pH 5 and dramatic swelling (Q > 200) was obtained at pH 7. At acidic pH, the hydrogen bonding interactions between the carboxylic acid and PEG ether groups are stable even in the aqueous environment and the polymer remains hydrophobic. Under neutral conditions, the acid groups are deprotonated, which disrupts hydrogen bonding and creates a hydrophilic material that swells to the limit of the crosslinked network. Multiple interrelated control parameters dictated by the synthetic recipe are available to separately control swelling and degradation rates of these novel polymers. Conclusions: Hydrolytically degradable polymers that respond to pH stimuli to activate the decomposition process have been developed and will be pursued for a variety of biomaterials applications. Support: Biosphere Medical