A subtle end-group effect on macroscopic physical gelation of triblock copolymer aqueous solutions.

During the last few decades, many researchers have investigated the self-assembly behavior of amphiphilic block copolymers. Most of these studies concerned nanostructures that resulted from self-assembly. In contrast, we have studied the end-group effect on the macroscopic self-assembly, which leads to formation of a biocompatible hydrogel. Although fruitful phenomena related to the end-group effect on microscopic molecular conformation and nanoscale aggregates have been observed in various organic molecules in selective solvents, reports of the end-group effect on the condensedstate behavior of self-assembled soft matter are rather limited. As a biomimetic wet material, polymeric hydrogel is a very important type of soft matter. Hydrogels capable of responding to external influences, such as temperature, pH, light, 11] counterion changes, biological molecules, and multiple factors, have been extensively investigated, as they have great potential value in drugdelivery systems and tissue engineering, sensors and valves, 21] surface patterning, and tunable optics. Some biodegradable/bioabsorbable hydrogels can form a gel in situ, and therefore are especially attractive as injectable biomaterials. Amorphous and biodegradable polymers with thermoinduced shape memory are also promising for use in minimally invasive surgery. Most hydrogels are formed by irreversible chemical cross-linking, but reversible physical gelation is another interesting topic in both fundamental research and potential applications. Recently, a few stimuliresponsive biodegradable physical gels have been reported in some multicomponent polymers, for instance, poly(ethylene glycol)–poly(a-hydroxy acid), poly(ethylene glycol)– polycaprolactone, chitosan–glycerol phosphate, and copolypeptides. Herein, we report the discovery that an alkyl end group can induce a thermoreversible physical gelation in an otherwise sol-like suspension. It is well-known that an end group with an opposite lyophilicity can lead to the formation of nanoparticles through self-assembly. Nevertheless, the alkyl end-group effect leading to macroscopic gelation reported herein is rather unique. Such a subtle effect for biodegradable synthetic molecules in water is very interesting and meaningful for biomaterials and other applications. A series of barbell-like ABA-type triblock copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid-co-glycolic acid) (PLGA), that is, PLGA-PEG-PLGAwith different end caps, were synthesized and characterized. PEG is hydrophilic, whereas PLGA is hydrophobic and biodegradable by the hydrolysis of ester bonds. Both PEG and PLGA are biocompatible and have been clinically used as implant biomaterials. The block copolymer composed of PLGA and PEG with the composition described is, by itself, not transformed into gels by changing the temperature, but we found that some of its derivatives exhibited a reversible sol–gel transition as a function of temperature. A very subtle endgroup effect on the macroscopic self-assembly of soft matter has thus been revealed. The mechanism of the underlying sol– gel transition is also discussed. The symmetric PLGA-PEG-PLGA copolymer with two hydroxy end groups (sample A) was synthesized by the ring-