**Injectable Thermosensitive Formulation Based on Polyurethane Hydrogel**/**Mesoporous Glasses for Sustained Co-Delivery of Functional Ions and Drugs**

**Monica Bo**ffi**to 1,**†**, Carlotta Pontremoli 2,**†**, Sonia Fiorilli 2,\*, Rossella Laurano 1, Gianluca Ciardelli 1,**‡ **and Chiara Vitale-Brovarone 2,**‡


Received: 7 August 2019; Accepted: 19 September 2019; Published: 1 October 2019

**Abstract:** Mini-invasively injectable hydrogels are widely attracting interest as smart tools for the co-delivery of therapeutic agents targeting different aspects of tissue/organ healing (e.g., neo-angiogenesis, inflammation). In this work, copper-substituted bioactive mesoporous glasses (Cu-MBGs) were prepared as nano- and micro-particles and successfully loaded with ibuprofen through an incipient wetness method (loaded ibuprofen approx. 10% *w*/*w*). Injectable hybrid formulations were then developed by dispersing ibuprofen-loaded Cu-MBGs within thermosensitive hydrogels based on a custom-made amphiphilic polyurethane. This procedure showed almost no effects on the gelation potential (gelation at 37 ◦C within 3–5 min). Cu2+ and ibuprofen were co-released over time in a sustained manner with a significantly lower burst release compared to MBG particles alone (burst release reduction approx. 85% and 65% for ibuprofen and Cu2+, respectively). Additionally, released Cu2+ species triggered polyurethane chemical degradation, thus enabling a possible tuning of gel residence time at the pathological site. The overall results sugges<sup>t</sup> that hybrid injectable thermosensitive gels could be successfully designed for the simultaneous localized co-delivery of multiple therapeutics.

**Keywords:** polyurethane; injectable hydrogels; ion/drug delivery; mesoporous bioactive glasses; tissue regeneration
