Thermoresponsive (co)polymers with LCST behavior based on a well-defined PiPOx scaffold showing high versatility in tuning up the TCP as well as the interval of response.

Synthetic polymers have had a major impact on the biomedical field. However, all polymers have their advantages and disadvantages, so that the selection of a certain polymeric material always is a compromise with regard to many properties, such as synthetic accessibility, solubility, thermal properties, biocompatibility and degradability. The development of novel polymers with superior properties for medical applications is the focus of many research groups. The present study highlights the use of poly(2-isopropenyl-2-oxazoline) (PiPOx), as biocompatible functional polymer to develop synthetic hydrogel materials using a simple straightforward synthesis protocol. A library of hydrogels was obtained by chemical cross-linking of PiPOx, using eight different non-toxic and bio-based dicarboxylic acids. The equilibrium swelling degree (ESD) of the final material can be modulated by simple modification of the composition of the reaction mixture, including the polymer concentration in the feed ratio between the 2-oxazoline pendent groups and the carboxylic acid groups as well as the cross-linker 2 length. The hydrogels with the highest water uptake were selected for further investigations regarding their potential use as biomaterials. We evaluated the thermoresponsiveness, the pH-degradability under physiological conditions and demonstrated proof-of-concept drug delivery experiments. The in vitro cellular studies demonstrated the noncytotoxic character of the PiPOx hydrogels, and its protein repellent properties, while mineralization studies revealed that such scaffolds do not promote mineralization/calcification phenomena. In view, of these results, these hydrogels show potential use as ophthalmologic materials or in drug delivery applications.