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.

A Mechanically Reinforced Super Bone Glue Makes a Leap in Hard Tissue Strong Adhesion and Augmented Bone Regeneration

“…It was also demonstrated that this hydrogel exhibited an incredibly strong adhesion strength with a variety of surfaces including PTFE, glass, bone, and tooth enamel. For example, in the case of bovine bone, the highest adhesion strength was >10 MPa (Figure 3A), which was significantly higher than the values reported in the literature for other adhesives [ 1,2,4b,22 ] and for the commercial bone glue CA. This strong adhesiveness observed for the L‐DPZ hydrogel was therefore attributed to several mechanisms (Figure 1B): 1) Physical interactions, such as π – π stacking and hydrogen bonding interactions caused by the presence of abundant free catechol groups on L‐DOPA; [ 17a ] 2) Chemical interactions between the catechol–quinone groups and the amine or thiol groups by means of Michael addition and Schiff‐base reactions; [ 9,17a ] 3) Intramolecular crosslinking between the polymer chains and intermolecular associations between the polymer and ZIF‐8; [ 17a,20b,25 ] and 4) Coordination bonds between the phenolic moieties of L‐DOPA and the Zn 2+ ions originating from ZIF‐8.…”

“…Thus, based on the excellent lap shear strength of the L‐DPZ2 hydrogel, its adhesion strength was compared with those of other adhesives reported in the literature. As shown in Figure 3C,D, the average adhesion strengths of the L‐DPZ2 hydrogel with the glass (Figure 3C) [ 21 ] and bovine bone (Figure 3D) [ 1,2,4b,22 ] substrates were significantly higher than those of the reported adhesives and the commercially available bone glue cyanoacrylate (CA). Subsequently, the adhesiveness of the L‐DPZ2 hydrogel was further assessed by means of a tensile adhesion test, and as a result, the tensile strength was calculated to be 3.42 ± 0.13 MPa; this value is significantly higher than those of the PVA, L‐DP, and L‐DPZ1 systems, which were 1.30 ± 0.09, 1.70 ± 0.07, and 2.32 ± 0.17 MPa, respectively (Figure 3E).…”

Bone-Adhesive Hydrogel for Effective Inhibition of M. tuberculosis and Osteoblast Regeneration

“…The faster gelation time of PNIPAM- co -GMA-CYS was mainly due to the higher formation of sulfhydryl groups. The CYS conjugation in the PNIPAM polymer forms a sulfhydryl chemical cross-linkage with vertebral column glycoproteins …”

Mechanism of Self-Healing Hydrogels and Application in Tissue Engineering

“…M. J et al [ 60 ] crosslinks N -hydroxysuccinimide-poly(2-oxazoline)s (Pox-NHS) and amine-poly(2-oxazoline)s/alendronate-poly(2-oxazoline)s (Pox-Ale) through Ca 2+ interact to form a hydrogel network. In addition, Ca 2+ can promote the repair of bone tissue to some extent.…”