Bone‐Adhesive Hydrogels Based on Dual Crosslinked Poly(2‐oxazoline)s

The development of bone glues based on bone‐adhesive hydrogels to allow for facile bone fracture fixation remains a major challenge. Herein, dual crosslinked hydrogels that combine tunable stiffness, ductility, and self‐healing capacity are successfully synthesized. The resulting double network hydrogel is formed by chemical crosslinking of N‐hydroxysuccinimide‐functionalized poly(2‐oxazoline)s(POx‐NHS)"?> with amine‐functionalized poly(2‐oxazoline)s, and physical crosslinking of alendronate‐functionalized poly(2‐oxazoline)s (POx‐Ale) with calcium ions in solution. The use of an excess of alendronate‐functionalized POx‐Ale polymers also ensures affinity toward calcium cations in the mineral phase of bone, thereby rendering these hydrogels adhesive to bone. The mechanical and bone‐adhesive properties of these novel hydrogels are superior to commercially available fibrin sealants. Moreover, hydrogels retain their bone‐adhesive properties under wet conditions. Although the dual crosslinked hydrogels swell considerably, they are stable upon immersion in phosphate‐buffered saline (up to 12 d) and even in ethylenediaminetetraacetic acid solution. The enhanced mechanical and bone‐adhesive properties of these hydrogels, as well as their in vitro stability, indicate that they have much application potential as bone‐adhesive glues. Dual crosslinked hydrogels that combine robust mechanical properties with bone adhesive behavior under wet conditions as well as in vitro stability are successfully synthesized. This novel bone adhesive hydrogel platform provides a strong basis for further development of bone adhesive glues to allow for facile bone fracture fixation.