Tailoring thermoresponsiveness of biocompatible polyethers: copolymers of linear glycerol and ethyl glycidyl ether.

Linear polyglycerol is known as a highly hydrophilic and biocompatible polymer that is currently considered for numerous medical applications. Derived from this well-known structure, the synthesis of highly biocompatible, thermoresponsive polyether copolymers via statistical anionic ring-opening copolymerization of ethyl glycidyl ether (EGE) and ethoxy ethyl glycidyl ether (EEGE) is described. Subsequent deprotection of the acetal groups of EEGE yields copolymers of linear glycerol (linG) and EGE, P(linG-co-EGE). These copolymers showed monomodal and narrow molecular weight distributions with dispersities D ≤ 1.07. The microstructure was investigated via in situ1H NMR kinetics experiments, revealing reactivity ratios of rEEGE = 1.787 ± 0.007 and rEGE = 0.560 ± 0.002, showing a slightly favored incorporation of EEGE over EGE. Due to the deliberate incorporation of rather hydrophobic EGE units into the water soluble linPG, tunable thermoresponsive behavior is achieved with cloud point temperatures Tcp between 9.0-71.4 °C. Besides the commonly utilized method turbidimetry, temperature-dependent 1H NMR measurements were used for more accurate and reproducible results. The change of the hydrodynamic radii rH of the copolymers and their aggregates upon reaching Tcp was investigated via DOSY NMR spectroscopy. To explore possible biomedical applications, as an example, the cell viability and immunology of an exemplary P(linG-co-EGE) copolymer sample was investigated. Since both, cell viability and immunology are comparable to the gold standard PEG, the herein presented copolymers show high potential as biocompatible and thermoresponsive alternatives to PEG for biomedical applications.

Polyethers Based on Short-Chain Alkyl Glycidyl Ethers: Thermoresponsive and Highly Biocompatible Materials.

The polymerization of short-chain alkyl glycidyl ethers (SCAGEs) enables the synthesis of biocompatible polyethers with finely tunable hydrophilicity. Aliphatic polyethers, most prominently poly(ethylene glycol) (PEG), are utilized in manifold biomedical applications due to their excellent biocompatibility and aqueous solubility. By incorporation of short hydrophobic side-chains at linear polyglycerol, control of aqueous solubility and the respective lower critical solution temperature (LCST) in aqueous solution is feasible. Concurrently, the chemically inert character in analogy to PEG is maintained, as no further functional groups are introduced at the polyether structure. Adjustment of the hydrophilicity and the thermoresponsive behavior of the resulting poly(glycidyl ether)s in a broad temperature range is achieved either by the combination of the different SCAGEs or with PEG as a hydrophilic block. Homopolymers of methyl and ethyl glycidyl ether (PGME, PEGE) are soluble in aqueous solution at room temperature. In contrast, n-propyl glycidyl ether and iso-propyl glycidyl ether lead to hydrophobic polyethers. The use of a variety of ring-opening polymerization techniques allows for controlled polymerization, while simultaneously determining the resulting microstructures. Atactic as well as isotactic polymers are accessible by utilization of the respective racemic or enantiomerically pure monomers. Polymer architectures varying from statistical copolymers, di- and triblock structures to star-shaped architectures, in combination with PEG, have been applied in various thermoresponsive hydrogel formulations or polymeric surface coatings for cell sheet engineering. Materials responding to stimuli are of increasing importance for "smart" biomedical systems, making thermoresponsive polyethers with short-alkyl ether side chains promising candidates for future biomaterials.

Frustrated Lewis Pair Polymers as Responsive Self-Healing Gels.

Steric bulk prevents the formation of strong bonds between Lewis acids and bases in frustrated Lewis pairs (FLPs), where latent reactivity makes these reagents transformative in small molecule activations and metal-free catalysis. However, their use as a platform for developing materials chemistry is unexplored. Here we report a fully macromolecular FLP, built from linear copolymers that containing either a sterically encumbered Lewis base or Lewis acid as a pendant functional group. The target functional copolymers were prepared by a controlled radical copolymerization of styrene with designer boron or phosphorus containing monomers. Mixtures of the B- and P-functionalized polystyrenes do not react, with the steric bulk of the functional monomers preventing the favorable Lewis acid base interaction. Addition of a small molecule (diethyl azodicarboxylate) promotes rapid network formation, cross-linking the reactive polymer chains. The resulting gel is dynamic, can self-heal, is heat responsive, and can be reshaped by postgelation processing.