Each year, millions of people suffer from complex bone fractures which require proper external or internal fixation. This fixation is usually achieved by means of devices such as plates, pins, and screws. These traditional fixation strategies are associated with severe drawbacks, which have prompted research and development of a variety of bone‐adhesive biomaterials as alternative. However, a clinically applicable bone‐adhesive biomaterial—in the form of a bone‐glue or bone‐adhesive membrane—that meets all requirements has not yet been identified. This perspective article discusses the current state of the art of bone‐adhesive materials with a particular focus on their clinical requirements, mechanisms of action, and future perspective. To develop adhesive biomaterials with specific affinity to bone tissue, a more rational design should be implemented. This perspective article is intended as a starting point and inspiration for future research and development of suitable bone‐adhesive materials.

In order to prevent hemorrhage during surgical procedures, a wide range of hemostatic agents have been developed. However, their efficacy is variable; hemostatic devices that use bioactive components to accelerate coagulation are dependent on natural sources, which limits reproducibility. Hybrid devices in which chain-end reactive poly(ethylene glycol) is employed as active component sometimes suffer from irregular cross-linking and dissolution of the polar PEG when blood flow is substantial. Herein, we describe a synthetic, nonbioactive hemostatic product by coating N-hydroxysuccinimide ester (NHS)-functional poly(2-oxazoline)s (POx-NHS) onto gelatin patches, which acts by formation of covalent cross-links between polymer, host blood proteins, gelatin and tissue to seal the wound site and prevent hemorrhage during surgery. We studied different process parameters (including polymer, carrier, and coating technique) in direct comparison with clinical products (Hemopatch and Tachosil) to obtain deeper understanding of this class of hemostatic products. In this work, we successfully prove the hemostatic efficacy of POx-NHS as polymer powders and coated patches both in vitro and in vivo against Hemopatch and Tachosil, demonstrating that POx-NHS are excellent candidate polymers for the development of next generation hemostatic patches.

A library of poly(2-oxazoline)s functionalized with controllable amounts of alendronate, hydroxyl, and carboxylic acid side groups was successfully synthesized to create novel polymers with tunable affinity for calcium cations. The affinity of alendronate-containing polymers for calcium cations was quantified using isothermal titration calorimetry. Thermodynamic measurements revealed that the Ca 2+ -binding affinity of these polymers increased linearly with the amount of alendronate functionalization, up to values ( K Ca 2+ = 2.4 × 10 5 M –1 ) that were about 120-fold higher than those for previously reported polymers. The calcium-binding capacity of alendronate-functionalized poly(2-oxazoline)s was exploited to form robust hydrogel networks cross-linked using reversible physical bonds. Oscillatory rheology showed that these hydrogels recovered more than 100% of their initial storage modulus after severe network destruction. The versatile synthesis of alendronate-functionalized polymers and their strong and tunable affinity for calcium cations render these polymers promising candidates for various biomedical applications.

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.