A thermo-sensitive poly(organophosphazene) hydrogel used as an extracellular matrix for artificial pancreas

Abstract

A poly(organophosphazene) bearing alpha-amino-omega-methyl-poly(ethylene glycol) (AMPEG) and hydrophobic L-isoleucine ethyl ester (IleOEt) side groups has been synthesized. This material exhibited 4 phase transitions in an aqueous solution on gradually increasing the temperature, i.e., a transparent sol, a transparent gel, an opaque gel and a turbid sol. A 10 wt% buffered solution of the polymer was employed to entrap islets of Langerhans in an artificial pancreas. Rat islets entrapped in the gel showed prolonged insulin secretion in response to basal (5.5 mM) glucose concentration compared to free rat islets and islets entrapped in other types of polymer gels. Over a 28-day culture period, the rat islets in the poly (organophosphazene) hydrogel maintained higher cell viability and insulin production versus rat islets in different hydrogels and free islets. This thermo-sensitive injectable, biodegradable matrix can be used with several cell types, including nerve cells, to promote nerve regeneration.