Drug-Releasing Tannic Acid-Mediated Adhesive PEG Hydrogel for Porous Titanium Implants

Porous titanium implants are commonly utilized for orthopedic surgery because they can mimic the mechanical properties and porous structure of human bone. However, the bio-inertness of titanium (Ti) has been reported to obstruct biointegration processes, resulting in slower bone repair. Here, we propose a localized drug delivery system on Ti surfaces using adhesive hydrogel to enhance biological-Ti interactions. The hydrogel was fabricated from polyethylene glycol (PEG), which was crosslinked by the complex of tannic acid (TA) and 1,4-phenylenediboronic acid (PDBA) and stabilized by bovine serum albumin (BSA). The hydrogel was formed and attached to a Ti plate to investigate stability, biodegradability, controlled drug release, and biocompatibility. The stability and biodegradability of the hydrogel could be tuned by adjusting the concentrations of BSA and TA. The hydrogel lasted and remained adhered to the Ti surface after being submerged in PBS for at least 15 days. The controlled release of strontium ranelate (SrRan) and the release mechanism depended on the amount of TA since it was found to govern the hydrogel integrity and pore size. Additionally, in vitro biocompatibility was validated using L929 fibroblast and MC3T3-E1 osteoblast cells that showed greater than 70% viability. The adhesive hydrogel was further studied by injecting it into a 3D-printed Ti-scaffold that contained porous structure mimicking natural human bone. The hydrogel completely filled and adhered to the inner porous structure of the scaffold. The biodegradation and drug release of the hydrogel in the scaffold occurred at a slower rate, suggesting a sustainable drug release that is suitable for bone cell regeneration. The overall results in biodegradability, controlled drug release, and biocompatibility demonstrate the great potential of the drug releasing TA-mediated adhesive PEG hydrogel as a Ti-enhancing biomaterial that supports osseointegration.