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

Abstract

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.

Keywords: alendronate; bone-adhesive; glues; hydrogels; poly(2-oxazoline)s.