Unlocking Potential: Ternary thiol-ene systems as clinically promising bone adhesives

Abstract

Introduction The number of bone fractures caused by physical trauma or overuse is steadily increasing as are the mandatory surgical procedures for their fixation.1 Since conventional fixation methods bring the drawback of potential infections and the need of removal surgeries, the adoption of a practical and biocompatible bone adhesive seems verry appealing to surgeons.2 However, there is no commercially available bone adhesive to date which fulfills all physico-chemical, biological and clinical requirements.3 Here, we elucidate the development of adhesive molecules called primers which facilitate binding to bone and implants. Together with thiol- ene matrices and photochemistry, we set stage for promising, light-curable bone adhesives.

Experimental Methods The primer synthesis, substrate (HAP and TiO2) preparation and shear bond strength measurements were performed as described in literature.4 For Ex- Vivo Indentation tests, circles with 8 mm diameter were excised and subsequently re-fixated using our bone adhesive formulation. Following indentation tests were performed with a digital force measuring device (Force Gauge SF-30 with a conical tip). In- vitro cytotoxicity of the vinyl compound TAI, the thiol TEMPIC and the primer 6C-diNB was tested in NCTC Clone 929 fibroblast cell culture using a Presto® Blue Assay according to ISO-10993- 5.

Results and Discussion Inspired by dental restorative materials we rely on thiol-ene photochemistry and chose thiols and vinyl compounds as matrix-monomers for the curable bone adhesive. Our bone adhesive formulation additionally contains primer molecules which ensure high bonding to the bone surface through their precisely chosen adhesion motif. The primers are additionally equipped with polymerizable groups for incorporation into the thiol-ene matrix, whereas a carbon spacer between the adhesion motif and the polymerizable group determines properties like solubility and hydrophilicity. Novel primer molecules differing in their polymerizable group and spacer length were synthesized and investigated, while phosphonic acid was chosen as adhesion motif. We observed an increase in the shear bond strength (SBS) with increasing number of polymerizable groups (n=2, di) and spacer length (6C) in the primer molecule. An outstanding SBS of 15.4 MPa was obtained with the primer Phn-6C-diNB bearing norbornenes as polymerizable groups, highlighting their high reactivity towards thiol- ene polymerization. Ex vivo indentation tests corroborate the superior performance of our bone adhesive and cytotoxicity tests confirm its benign nature.

Conclusions By careful design of the primer molecule, we successfully developed the first known, time- efficient and surgically preferred one-step light-curable bone adhesive. Remarkable shear bond strengths and first ex vivo studies underline its potential for treatment of comminuted fractures and fixation of small bone fragments.