Catechol- and thiol-containing binder that aggregates granular xenografts in reconstructed bone defects by mimicking mussel wet adhesion

Xenograft bone granules are bone graft materials that are widely used to reconstruct bone tissue in clinical practice, and their clinical success requires aggregation with a biocompatible binder. While the catechol mussel bioadhesive has been used as a key universal biomedical glue moiety, the thiols in mussel adhesive proteins have recently been shown to play key roles in mussel wet adhesion. Here, pentaerythritol tris(3-mercaptopropionate)-di-catechol (PETMP-di-catechol), a catechol- and thiol-containing binder molecule that mimics mussel adhesive proteins, was used to aggregate xenograft bone granules and reconstruct bone tissue. The PETMP-di-catechol-aggregated xenograft bone granules were most resistive to compression stress when both the catechol and thiol moieties in PETMP-di-catechol were chemically oxidized with sodium periodate. The xenograft bone granules aggregated with the oxidized PETMP-di-catechol exhibited enhanced osteogenic cellular behavior in vitro and in vivo in a rat calvarial defect model, compared to the control group treated with catechol-conjugated chitosan, a catechol-containing polymer binder devoid of thiol moieties. Hence, the thiol-containing catechol-functionalized binder exhibits improved bone tissue reconstruction properties by mimicking mussel wet adhesion. In addition, our study suggests that PETMP-di-catechol is a potential biocompatible bone binder for use in clinical settings.