Sterilizable Gels from Thermoresponsive Block Copolymer Worms

Abstract

Biocompatible hydrogels have many applications, ranging from contact lenses to tissue engineering scaffolds. In most cases, rigorous sterilization is essential. Herein we show that a biocompatible diblock copolymer forms wormlike micelles via polymerization-induced self-assembly in aqueous solution. At a copolymer concentration of 10.0 w/w %, interworm entanglements lead to the formation of a free-standing physical hydrogel at 21 °C. Gel dissolution occurs on cooling to 4 °C due to an unusual worm-to-sphere order-order transition, as confirmed by rheology, electron microscopy, variable temperature (1)H NMR spectroscopy, and scattering studies. Moreover, this thermo-reversible behavior allows the facile preparation of sterile gels, since ultrafiltration of the diblock copolymer nanoparticles in their low-viscosity spherical form at 4 °C efficiently removes micrometer-sized bacteria; regelation occurs at 21 °C as the copolymer chains regain their wormlike morphology. Biocompatibility tests indicate good cell viabilities for these worm gels, which suggest potential biomedical applications.

A Vesicle‐to‐Worm Transition Provides a New High‐Temperature Oil Thickening Mechanism

“…Moreover, a thermally‐triggered worm‐to‐sphere transition results in rapid in situ degelation 13, 14. A 10 % w/w dispersion of PSMA 13 ‐PBzMA 96 vesicles in mineral oil was studied to assess the effect of the vesicle‐to‐worm transition on its rheological behavior (see Figure 5).…”

“…There are rather few literature examples of significantly higher viscosities being achieved on increasing the solution temperature, with most of these studies involving aqueous formulations 13, 20. However, these thermal transitions typically occur at relatively low temperatures (4 °C to 30 °C) and usually increase the aqueous solution viscosity by less than an order of magnitude.…”

Combining Biomimetic Block Copolymer Worms with an Ice‐Inhibiting Polymer for the Solvent‐Free Cryopreservation of Red Blood Cells

“…More specifically, RAFT aqueous dispersion polymerization of HPMA was conducted using a PGMA 56 macro‐CTA (CTA=chain transfer agent) to target PGMA 56 ‐PHPMA 155 worms, as previously reported by Armes and co‐workers (see the Supporting Information for further experimental and characterization details) 11a, 12. These worm gels exhibited thermoresponsive behavior, undergoing degelation upon cooling to 5–10 °C by a reversible worm‐to‐sphere transition 11a. This order–order morphological transformation may provide a useful trigger for the construction of 3D cell‐seeded gels (see below).…”

Disulfide-Based Diblock Copolymer Worm Gels: A Wholly-Synthetic Thermoreversible 3D Matrix for Sheet-Based Cultures

“…[13] In particular, polymerization-induced selfassembly (PISA) of poly(glycerol monomethacrylate)-block-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) diblock copolymers enables well-defined spheres, worms or vesicles to be produced at high solids, simply by targeting the appropriate diblock composition. [14,15] The worm morphology is of particular interest, because these highly anisotropic particles form soft, free-standing aqueous gels. [15,16] These worm gels are thermoresponsive: upon cooling to 5 °C, the hydrophobic core-forming PHPMA block becomes more plasticized by water, which induces a worm-to-sphere transition and causes de-gelling (i.e., separation of fused spheres).…”

“…[14,15] The worm morphology is of particular interest, because these highly anisotropic particles form soft, free-standing aqueous gels. [15,16] These worm gels are thermoresponsive: upon cooling to 5 °C, the hydrophobic core-forming PHPMA block becomes more plasticized by water, which induces a worm-to-sphere transition and causes de-gelling (i.e., separation of fused spheres). The resulting low-viscosity fluid is amenable to cold ultrafiltration, which provides a facile route to sterilization.…”